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Background: Depression is one of the most common psychiatric disorders worldwide and causes disability. There is a need to produce new agents for the treatment of depression with the maximum efficiency and the lowest side effects. The positive effects of Pistacia lentiscus have been reported in the central nervous system and different disorders. Objectives: This study evaluated the antidepressant-like effect of the ethanolic extract of P. lentiscus (EEPL) in a mouse model and its possible mechanisms. Methods: The male NMRI mice (20 - 25 g) intraperitoneally (i.p.) received vehicle (10 mL/kg), imipramine (30 mg/kg), fluoxetine (20 mg/kg, i.p.), and EEPL (50 - 400 mg/kg). After 45 minutes, the animals were subjected to a tail suspension test (TST). The open-filed test (OFT) was used to assess the animal's locomotion. To elucidate possible monoaminergic mechanisms, the mice were pre-treated with various receptor antagonists 1 hour before the most effective dose of EEPL. Results: The administration of EEPL (100 - 400 mg/kg) induced an antidepressant-like effect (37.5%, 49.3%, and 63.9% reduction, respectively) in the TST (P < 0.001) without considerable effects on animal locomotion in OFT (P > 0.05). The antidepressant-like effect of EEPL (200 mg/kg) was blocked by the pre-treatment of animals with SCH23390, sulpiride, haloperidol, ketanserin, WAY100135, and p-chlorophenylalanine (pCPA) (P < 0.001), but not with prazosin, yohimbine, or propranolol (P > 0.05). Conclusions: The results show that the antidepressant-like effect of EEPL is mediated by the modulation of dopaminergic and serotonergic systems. Overall, the results suggested that EEPL exerted an antidepressant-like activity in the mouse model of depression, which might be considered a useful drug in the management of depression. [ABSTRACT FROM AUTHOR]

Major depression is one of the most common psychiatric disorders worldwide, usually associated with anxiety. The multi-etiological nature of depression has increased the search for new antidepressant molecules, including irisin, for which, in a previous study, we tested its effect in young mice when administered intraperitoneally in a long-term intermittent manner. Here, we evaluated the effect of subcutaneous short-term irisin administration (100 µg/Kg/day/5 days) in male and female mice subjected to behavioral paradigms: Tail Suspension Test (TST), Forced Swim Test (FST), Elevated Plus Maze (EPM), and Y Maze (YM). Moreover, a qRT-PCR assay was performed to analyze the impact of irisin treatment on Pgc-1α/FNDC5 expression in the brain. A significant reduction in immobility time in TST and FST was observed in irisin-treated mice. Furthermore, irisin treatment significantly increased the number of entries and time spent in open arms, demonstrating its anxiolytic effect. Memory-enhancing effects were not reported in YM. Interestingly, no gender differences were observed in all behavioral tests. Overall, these results suggest that short-term subcutaneous irisin administration can exert an antidepressant and anxiolytic role, probably due to the activation of the Pgc-1α/FNDC5 system in the brain. Further investigation could lead to the identification of irisin as a new agent for the treatment of psychiatric disorders. [ABSTRACT FROM AUTHOR]

Depression is a serious psychological disorder which negatively affects human feelings and actions. The use of antidepressants is the therapy of choice while treating depression. However, such drugs are associated with severe side effects. There is a need for efficient and harmless drugs. In this connection, the present study was designed to synthesize several substituted benzodiazepine derivatives and explore their antidepressant potentials in an animal model. The chalcone backbone was initially synthesized, which was then converted into several substituted benzodiazepine derivatives designated as 1–6. The synthesized compounds were identified using spectroscopic techniques. The experimental animals (mice) after acclimatation were subjected to forced swim test (FST) and tail suspension test (TST) after oral administration of the synthesized compounds to evaluate their antidepressant potentials. At the completion of the mentioned test, the animals were sacrificed to determine GABA level in their brain hippocampus. The chloro-substituent compound (2) significantly reduced the immobility time (80.81 ± 1.14 s; p < 0.001 at 1.25 mg/kg body weight and 75.68 ± 3.73 s with p < 0.001 at 2.5 mg/kg body weight dose), whereas nitro-substituent compound (5) reduced the immobility time to 118.95 ± 1.31 and 106.69 ± 3.62 s (p < 0.001), respectively, at the tested doses (FST). For control groups, the recorded immobility time recorded was 177.24 ± 1.82 s. The standard drug diazepam significantly reduced immobility time to 70.13 ± 4.12 s while imipramine reduced it to 65.45 ± 2.81 s (p < 0.001). Similarly, in the TST, the compound 2 reduced immobility time to 74.93 ± 1.14 s (p < 0.001) and 70.38 ± 1.43 s (p < 0.001), while compound 5 reduced it to 88.23 ± 1.89 s (p < 0.001) and 91.31 ± 1.73 s (p < 0.001) at the tested doses, respectively, as compared to the control group immobility time (166.13 ± 2.18 s). The compounds 1, 3, 4, and 6 showed weak antidepressant responses as compared to compounds 2 and 5. The compounds 2 and 5 also significantly enhanced the GABA level in the brain's hippocampus of experimental animals, indicating the possible involvement of GABAergic mechanism in alleviating the depression which is evident from the significant increase in mRNA levels for the α subunit of the GABAA receptors in the prefrontal cortex of mice as well. From the results, it can be concluded that compound 2 and 5 could be used as alternative drugs of depression. However, further exploration in this connection is needed in other animal models in order to confirm the observed results in this study. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Depression is one of the five major causes of the global burden of diseases. Currently available antidepressants have low efficacy, slow onset, and serious side effects, while exercise is a better way to treat depression. This paper systematically evaluates the effects of exercise on depression-related behaviors in chronic unpredictable mild stress (CUMS) animal models. METHODS: A systematic literature search from January 1, 2000 to February 28, 2022 was performed in WanFang, CNKI, PubMed, Embase, and Web of Science databases. Studies regarding the effects of treadmill running, swimming, and voluntary wheel running on forced swimming, tail suspension, and sugar water preference behavior of CUMS animal models were collected. Literature screening, data extraction and methodological quality assessments were completed by two researchers independently. The SYRCLE tool was used to assess the risk of bias in the included studies. RevMan 5.3 and Stata 13.0 analysis software were used for statistical analysis. RESULTS: A total of 23 controlled experimental studies were included, including 301 rodents in exercise group and 302 rodents in control group. Meta-analysis results showed that exercise significantly reduced the forced swimming latency [standardized mean difference (SMD)=-3.93, 95% confidence interval (CI): (-4.88, -2.98), P < 0.000 01] and tail suspension latency [SMD=-4.42, 95% CI: (-5.62, -3.23), P < 0.000 01] in CUMS modeling rats and mice. Exercise also increased the index of sucrose preference test [SMD=2.37, 95% CI: (1.62, 3.11), P < 0.000 01]. Subgroup analysis of exercise modes in the suspension test reduced heterogeneity [SMD=-3.68, 95% CI: (-4.16, -3.21), P < 0.000 01], but it did not affect the exercise effect. CONCLUSION: Exercise can effectively improve depression-like behaviors of forced swimming, tail suspension, and sucrose preference tests in CUMS model rodents. The mode of exercise may be the source of heterogeneity affecting the behavior of the suspension tail test. Modeling time, exercise stage, exercise mode, and exercise duration are not the main factors that affect the effect of exercise on depression. [ABSTRACT FROM AUTHOR]

Hypothyroidism is closely related to mental disorders, mainly depression, through an as-yet-unknown mechanism. The cerebral inflammatory immune process has been implied to play a pivotal role in the onset of affective symptoms in several conditions. In order to gain insight into the mechanism underlying the depressive behaviors in hypothyroid rats, brain microglial activation was evaluated using micro positron emission tomography imaging with a translocator protein (TSPO) radioligand. Hypothyroidism was induced in adult male Wistar rats by administration of 0.05% propylthiouracil in drinking water for five weeks. Open field, forced swimming and tail suspension tests were employed to evaluate the depressive behavior in hypothyroid rats, and the relationship between the behavioral changes and brain microglial activation was evaluated using [18F] DPA-714 micro positron emission tomography imaging. The open field test revealed significantly reduced first-minute activity and rearing behavior in the hypothyroid group, as well as significantly increased immobility in the forced swimming test and the tail suspension test. Hypothyroidism induced significantly increased microglial activation in the hippocampus. The radioligand uptake in the hippocampus correlated negatively with first-minute activity in the open field test (p < 0.05), and the radioligand uptake in the hippocampus correlated positively with changes in the immobility time in the forced swimming test and the tail suspension test (p < 0.05). Immunohistochemistry also confirmed the activation of microglia and inflammatory bodies in hypothyroid rats. The results indicate that hypothyroidism can induce depressive behavior in adult Wistar rats, microglial activation in the hippocampus plays an important role in the depressive behavior in hypothyroid rats and the inflammatory immune mechanism may underlie the behavioral abnormalities in thyroid dysfunction. Furthermore, the findings in the present study suggest there might be a common mechanism underlying depressive behavior in adult-onset hypothyroidism and depression. [ABSTRACT FROM AUTHOR]

Mangifera indica L., also known as mango, is a tropical fruit that belongs to the Anacardiaceae family and is prized for its juiciness, unique flavour, and worldwide popularity. The current study aimed to probe into antidepressant power (ADP) of MIS in animals and confirmation of ADP with in silico induced-fit molecular docking. The depression model was prepared by exposing mice to various stressors from 9:00 am to 2:00 pm during 42 days study period. MIS extract and fluoxetine were given daily for 30 min before exposing animals to stressors. ADP was evaluated by various behavioural tests and biochemical analysis. Results showed increased physical activity in mice under behavioural tests, plasma nitrite and malondialdehyde (MDA) levels and monoamine oxidase A (MAO-A) activity decreased dose-dependently in MIS treated mice and superoxide dismutases (SOD) levels increased in treated groups as compared to disease control. With the peculiar behaviour and significant interactions of the functional residues of target proteins with selected ligands along with the best absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, it is concluded that catechin could be the best MAO-A inhibitor at a binding energy of -8.85 kcal/mol, and two hydrogen bonds were generated with Cys406 (A) and Gly443 (A) residues of the active binding site of MAO-A enzyme. While catechin at -6.86 kcal/mol generated three hydrogen bonds with Ala263 (A) and Gly434 (A) residues of the active site of monoamine oxidase B (MAO-B) enzyme and stabilized the best conformation. Therefore, it is highly recommended to test the selected lead-like compound catechin in the laboratory with biological system analysis to confirm its activity as MAO-A and MAO-B inhibitors so it can be declared as one of the novel therapeutic options with anti-depressant activity. Our findings concluded that M. indica seeds could be a significant and alternative anti-depressant therapy. [ABSTRACT FROM AUTHOR]

Rationale: Depression is a mental disorder that affects approximately 280 million people worldwide. In the search for new treatments for mood disorders, compounds containing selenium and indolizine derivatives show promising results. Objectives and methods: To evaluate the antidepressant-like effect of 1-(phenylselanyl)-2-(p-tolyl)indolizine (MeSeI) (0.5–50 mg/kg, intragastric—i.g.) on the tail suspension test (TST) and the forced swim test (FST) in adult male Swiss mice and to elucidate the role of the serotonergic system in this effect through pharmacological and in silico approaches, as well to evaluate acute oral toxicity at a high dose (300 mg/kg). Results: MeSeI administered 30 min before the FST and the TST reduced immobility time at doses from 1 mg/kg and at 50 mg/kg and increased the latency time for the first episode of immobility, demonstrating an antidepressant-like effect. In the open field test (OFT), MeSeI did not change the locomotor activity. The antidepressant-like effect of MeSeI (50 mg/kg, i.g.) was prevented by the pre-treatment with p-chlorophenylalanine (p-CPA), a selective tryptophan hydroxylase inhibitor (100 mg/kg, intraperitoneally—i.p. for 4 days), with ketanserin, a 5-HT2A/2C receptor antagonist (1 mg/kg, i.p.), and with GR113808, a 5-HT4 receptor antagonist (0.1 mg/kg, i.p.), but not with WAY100635, a selective 5-HT1A receptor antagonist (0.1 mg/kg, subcutaneous—s.c.) and ondansetron, a 5-HT3 receptor antagonist (1 mg/kg, i.p.). MeSeI showed a binding affinity with 5-HT2A, 5 -HT2C, and 5-HT4 receptors by molecular docking. MeSeI (300 mg/kg, i.g.) demonstrated low potential to cause acute toxicity in adult female Swiss mice. Conclusion: In summary, MeSeI exhibits an antidepressant-like effect mediated by the serotonergic system and could be considered for the development of new treatment strategies for depression. [ABSTRACT FROM AUTHOR]

This study aimed to examine the antidepressant properties of apigenin in an experimental mouse model of chronic mild stress (CMS). Three weeks following CMS, albino mice of either sex were tested for their antidepressant effects using the tail suspension test (TST) and the sucrose preference test. The percentage preference for sucrose solution and the amount of time spent immobile in the TST were calculated. The brain malondialdehyde (MDA) levels, catalase activity, and reduced glutathione levels were checked to determine the antioxidant potential of treatments. When compared to the control, animals treated with apigenin during the CMS periods showed significantly shorter TST immobility times. Apigenin administration raised the percentage preference for sucrose solution in a dose-dependent manner, which put it on par with the widely used antidepressant imipramine. Animals treated with apigenin displayed a significantly (p ˂ 0.05) greater spontaneous locomotor count (281) when compared to the vehicle-treated group (245). Apigenin was also highly effective in significantly (p ˂ 0.01) lowering plasma corticosterone levels (17 vs. 28 µg/mL) and nitrite (19 vs. 33 µg/mL) produced by CMS in comparison to the control group. During CMS, a high dose (50 mg/kg) of apigenin was given, which greatly increased the reduced glutathione level while significantly decreasing the brain's MDA and catalase activity when compared to the control group. As a result, we infer that high doses of apigenin may have potential antidepressant effects in animal models via various mechanisms. [ABSTRACT FROM AUTHOR]

Context: Michelia champaca L. (Magnoliaceae) has been known since ancient times for its rich medicinal properties. Objective: The ethanol extract of Michelia champaca leaves (EEMC) was evaluated on depression and anxiety using in vivo and in silico studies Materials and methods: Swiss albino mice were divided into control, standard, 100 and 200 mg/kg b.w. EEMC groups and for drug administration using oral gavage. The antidepressant activity was evaluated using forced swim test (FST) and tail suspension test (TST) whereas the anxiolytic activity through elevated plus maze and light and dark tests. The in silico studies included molecular docking against human potassium channel KCSA-FAB and human serotonin transporter, and ADME/T analysis. Results: Open arm duration and entries were comparable between 200mg/kg b.w. group (184.45 ± 1.00 s and 6.25 ± 1.11, respectively) and that of diazepam treated group (180.02 s ± 0.40 and 6.10 ± 0.05, respectively). Time spent in the light cubicle was higher (46.86 ± 0.03%), similar to that of diazepam (44.33 ± 0.64%), suggesting its potent anxiolytic activity. A delayed onset of immobility and lowered immobility time was seen at both the treatment doses (FST: 93.7 ± 1.70 and 89.1 ± 0.40 s; TST: 35.05 ± 2.75 and 38.50 ± 4.10 s) and the standard drug imipramine (FST: 72.7 ± 3.72 and TST: 30.01 ± 2.99 s), indicative of its antidepressant ability. In silico studies predicted doripenem to induce anxiolytic and antidepressant activity by inhibiting human potassium channel KCSA-FAB and human serotonin transporter proteins, respectively. Conclusions: EEMC is a rich source of bioactive compounds with strong antidepressant and anxiolytic properties. [ABSTRACT FROM AUTHOR]

Animal models of early adversity or neurodevelopmental disorders are associated with altered parvalbumin (PV)-positive inhibitory interneuron number and function, correlated with a dysregulated excitation–inhibition (E/I) balance that is implicated in the pathophysiology of neuropsychiatric disorders. We sought to address whether altering neuronal activity of PV-positive interneurons during the postnatal developmental window influences the emergence of anxio-depressive behaviors in adulthood, which are known to be perturbed in models of early adversity and neurodevelopmental disorders. We used a PV-Cre::hM3Dq-DREADD bigenic mouse line that selectively expresses the hM3Dq-DREADD receptor in PV-positive interneurons, and chemogenetically enhanced Gq signaling in PV-positive interneurons during the postnatal window via administration of the DREADD agonist, clozapine-N-oxide. Immunofluorescence studies have indicated the selective expression of hM3Dq-DREADD in PV-positive interneurons in limbic circuits, and have revealed a reduction in expression of the neuronal activity marker, c-Fos, in these circuits, following chemogenetic hM3Dq-DREADD-mediated activation of PV-positive inhibitory interneurons. We noted no change in either growth or sensorimotor reflex milestones following chronic hM3Dq-DREADD-mediated chemogenetic activation of PV-positive inhibitory interneurons in postnatal life. Adult male and female PV-Cre::hM3Dq-DREADD bigenic mice with a history of postnatal chemogenetic activation of PV-positive interneurons exhibited a reduction in anxiety and despair-like behavior in adulthood, which was noted in both a behavioral task- and sex-dependent manner. These results indicate that altering neuronal activity within PV-positive interneurons during the critical postnatal developmental window can shape the emergence of anxio-depressive behaviors in adulthood, with sex as a variable playing a key role in determining behavioral outcomes. [ABSTRACT FROM AUTHOR]

Medicinal plants belonging to the Verbenaceae family demonstrated antidepressant effects in preclinical studies. Depression is one of the largest contributors to the global health burden of all countries. Plants from the Aloysia genus are traditionally used for affective disorders, and some of them have proven anxiolytic and antidepressant activity. The aim of this work was to evaluate the antidepressant effect of the ethanolic extract of Aloysia gratissima var. gratissima (Agg) and Aloysia virgata var. platyphylla (Avp) in mice. A tail suspension test (TST) and forced swimming test (FST) were conducted after three doses in a period of 24 h and after 7 days of treatment. Imipramine was used as an antidepressant drug. The main results demonstrated that Agg extract reduced the immobility time in mice treated orally for 7 consecutive days when compared to the control group (reduced by about 77%, imipramine 70%). Animals treated with three doses of Avp in a 24-h period had reduced immobility time in the FST (60%), and after 7 days of treatment the reduction was greater (Avp 50, 100, and 200 about 85%; Avp 400, 96.5%; p < 0.0001, imipramine, 77%). LCMS analysis showed the presence of verbascoside, hoffmaniaketone, and hoffmaniaketone acetate in both, A. virgata var. platyphylla and A. gratissima var gratissima. The flavonoids nepetin and 6-hydroxyluteolin were also found in Agg. Both tested extracts demonstrated promising antidepressant-like activity in mice. [ABSTRACT FROM AUTHOR]

Background and Objectives: Oxidative stress plays an important role in the pathophysiology of many diseases, including depression. On the other hand, previous studies have reported the antioxidant effect of Tanacetum balsamita. The aim of the present study is to investigate the antidepressant effect of Tanacetum balsamita essential oil (TBEO) in animal models of depression. Materials and Methods: In this experimental study, 84 mice were randomly divided into 14 groups of 6 and intraperitoneally received vehicle (10 ml/kg), fluoxetine (20 mg/kg), imipramine (30 mg/kg), and TBEO (12.5, 50,100, and 200mg/kg). To evaluate the antidepressant effect, the forced swimming test (FST) and tail suspension test (TST) were used. The animal locomotion was also assessed by open-field test (OFT). Data were analyzed using one-way analysis of variance followed by the Newman-Keuls post hoc test. Results: Doses of 50 to 100 mg/kg of essential oil in both FST and TST caused a significant reduction in the duration of immobility (p<0.001). In addition, doses of 50,100 and 200 mg/kg of TBEO significantly increased swimming time (p<0.001). But, climbing time was not significantly increased by all doses of the essential oil (p>0.05). Also, none of the essential oil doses caused a significant change in the number of crossing and rearing's in the OFT (p>0.05). Conclusion: Tanacetum balsamita essential oil has an anti-depressant effect in mice. Nevertheless, more studies are needed to determine its mechanism of action. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the antidepressant property of crocin (Crocetin digentiobiose ester) using a chronic mild stress (CMS)-induced depression model in experimental mice. The tail suspension test (TST) and the sucrose preference test were used to evaluate the antidepressant effect on albino mice of either sex after three weeks of CMS. The period of immobility in the TST and percentage preference for sucrose solution were recorded. By monitoring brain malondialdehyde (MDA) level, catalase (CAT) activity, and reduced glutathione (GSH) level, the antioxidant potential was assessed. Three dosages of crocin (4.84, 9.69, and 19.38 mg/kg) were evaluated. When compared to controls, animals that received crocin administration during three periods of CMS had considerably shorter immobility times during the TST. Crocin treatment also raised the percentage preference for sucrose solution in a dose-dependent manner, bringing it to parity with the conventional antidepressant, imipramine. Animals that received a high dose of crocin had a much greater spontaneous locomotor activity. Furthermore, a high dose of crocin remarkably lowered plasma corticosterone and nitrite levels brought on by CMS. Additionally, high doses of crocin given during CMS greatly enhanced reduced glutathione levels while considerably reducing the brain's MDA and catalase activities. In conclusion, high doses of crocin may have an antidepressant effect in an animal model through several mechanisms. However, further studies should be carried out to explore the role of neurotransmitters for their antidepressant property. [ABSTRACT FROM AUTHOR]

Plasma membrane monoamine transporter (PMAT, Slc29a4) transports monoamine neurotransmitters, including dopamine and serotonin, faster than more studied monoamine transporters, e.g., dopamine transporter (DAT), or serotonin transporter (SERT), but with ~400–600-fold less affinity. A considerable challenge in understanding PMAT's monoamine clearance contributions is that no current drugs selectively inhibit PMAT. To advance knowledge about PMAT's monoamine uptake role, and to circumvent this present challenge, we investigated how drugs that selectively block DAT/SERT influence behavioral readouts in PMAT wildtype, heterozygote, and knockout mice of both sexes. Drugs typically used as antidepressants (escitalopram, bupropion) were administered acutely for readouts in tail suspension and locomotor tests. Drugs with psychostimulant properties (cocaine, D-amphetamine) were administered repeatedly to assess initial locomotor responses plus psychostimulant-induced locomotor sensitization. Though we hypothesized that PMAT-deficient mice would exhibit augmented responses to antidepressant and psychostimulant drugs due to constitutively attenuated monoamine uptake, we instead observed sex-selective responses to antidepressant drugs in opposing directions, and subtle sex-specific reductions in psychostimulant-induced locomotor sensitization. These results suggest that PMAT functions differently across sexes, and support hypotheses that PMAT's monoamine clearance contribution emerges when frontline transporters (e.g., DAT, SERT) are absent, saturated, and/or blocked. Thus, known human polymorphisms that reduce PMAT function could be worth investigating as contributors to varied antidepressant and psychostimulant responses. [ABSTRACT FROM AUTHOR]

The therapy of depression is challenging and still unsatisfactory despite the presence of many antidepressant drugs on the market. Consequently, there is a continuous need to search for new, safer, and more effective antidepressant therapeutics. Previous studies have suggested a potential association of brain histaminergic/serotoninergic signaling and antidepressant- and anxiolytic-like effects. Here, we evaluated the in vivo antidepressant- and anxiolytic-like effects of the newly developed multiple-active ligand ST-2300. ST-2300 was developed from 5-HT2A/2C inverse agonist pimavanserin (PIM, ACP-103) and incorporates a histamine H3 receptor (H3R) antagonist pharmacophore. Despite its parent compound, ST-2300 showed only moderate serotonin 5-HT2A antagonist/inverse agonist affinity (Ki value of 1302 nM), but excellent H3R affinity (Ki value of 14 nM). In vivo effects were examined using forced swim test (FST), tail suspension test (TST), and the open field test (OFT) in C57BL/6 mice. Unlike PIM, ST-2300 significantly increased the anxiolytic-like effects in OFT without altering general motor activity. In FST and TST, ST-2300 was able to reduce immobility time similar to fluoxetine (FLX), a recognized antidepressant drug. Importantly, pretreatment with the CNS-penetrant H3R agonist (R)-α-methylhistamine reversed the antidepressant-like effects of ST-2300 in FST and TST, but failed to reverse the ST-2300-provided anxiolytic effects in OFT. Present findings reveal critical structural features that are useful in a rational multiple-pharmacological approach to target H3R/5-HT2A/5-HT2C. [ABSTRACT FROM AUTHOR]

Depression is pleiotropic and influenced by diverse genetic, environmental, and pharmacological factors. Identifying patterns of circuit activity on which many of these factors converge would be important, because studying these patterns could reveal underlying pathophysiological processes and/or novel therapies. Depression is commonly assumed to involve changes within prefrontal circuits, and dopamine D 2 receptor (D2R) agonists are increasingly used as adjunctive antidepressants. Nevertheless, how D2Rs influence disease-relevant patterns of prefrontal circuit activity remains unknown. We used brain slice calcium imaging to measure how patterns of prefrontal activity are modulated by D2Rs, antidepressants, and manipulations that increase depression susceptibility. To validate the idea that prefrontal D2Rs might contribute to antidepressant responses, we used optogenetic and genetic manipulations to test how dopamine, D2Rs, and D2R+ neurons contribute to stress-coping behavior. Patterns of positively correlated activity in prefrontal microcircuits are specifically enhanced by D2R stimulation as well as by two mechanistically distinct antidepressants, ketamine and fluoxetine. Conversely, this D2R-driven effect was disrupted in two etiologically distinct depression models, a genetic susceptibility model and mice that are susceptible to chronic social defeat. Phasic stimulation of dopaminergic afferents to the prefrontal cortex and closed-loop stimulation of D2R+ neurons increased effortful responses to tail suspension stress, whereas prefrontal D2R deletion reduced the duration of individual struggling episodes. Correlated prefrontal microcircuit activity represents a point of convergence for multiple depression-related manipulations. Prefrontal D2Rs enhance this activity. Through this mechanism, prefrontal D2Rs may promote network states associated with antidepressant actions and effortful responses to stress. [ABSTRACT FROM AUTHOR]

Schizophrenia is a serious psychiatric disorder that affects the social life of patients. Psychiatric disorders are caused by a complex combination of genetic (G) and environmental (E) factors. Polysialylation represents a unique posttranslational modification of a protein, and such changes in neural cell adhesion molecules (NCAMs) have been reported in postmortem brains from patients with psychiatric disorders. To understand the G × E effect on polysialylated NCAM expression, in this study, we performed precise measurements of polySia and NCAM using a disrupted-in-schizophrenia 1 (DISC1)-mutant mouse (G), a mouse model of schizophrenia, under acute stress conditions (E). This is the first study to reveal a lower number and smaller length of polySia in the suprachiasmatic nucleus of DISC1 mutants relative to those in wild-type (WT) mice. In addition, an analysis of polySia and NCAM responses to acute stress in five brain regions (olfactory bulb, prefrontal cortex, suprachiasmatic nucleus, amygdala, and hippocampus) revealed that the pattern of changes in these responses in WT mice and DISC1 mutants differed by region. These differences could indicate the vulnerability of DISC1 mutants to stress. [ABSTRACT FROM AUTHOR]

Background: Gentisic acid has been reported to show neuroprotective effect. But its effect on depression is not available in the literature. So we evaluated the effect of this compound on depressive behavior in unstressed (normal) mice and stressed mice. Materials and Methods: Swiss albino male mice were given unpredictable mild stressors for twenty-one consecutive days to produce depressive behavior. Gentisic acid (25, 50, 100 mg/kg) and fluoxetine (20 mg/kg) were administered orally for twenty-one consecutive days. Depressive behavior was detected by tail suspension test and sucrose preference test. After behavioral testing, biochemical estimations were performed in plasma and brain. Histopathological studies on brain were also performed. Results: Immobility time of mice in tail suspension test was remarkably decreased by gentisic acid (50 and 100 mg/kg). Gentisic acid also restored decreased sucrose preference in mice subjected to stress paradigm. It remarkably lowered concentration of plasma nitrite, brain monoamine oxidase-A, malondialdehyde, TNF-a; and increased concentration of catalase and GSH in normal mice and also stressed mice. It also remarkably lowered plasma corticosterone concentration in stressed mice. Histopathological studies indicated protection by gentisic acid against hyperchromatic nuclei in brain. Conclusion: Gentisic acid produced remarkable antidepressant effect in normal mice and also stressed mice. The possible mechanisms for the observed antidepressant effect of gentisic acid might be through inhibition of brain MAO-A, amelioration of neuroinflammation and oxidative stress; and protection against hyperchromatic nuclei in brain. Moreover, antidepressant effect of gentisic acid in stressed mice might be through lowering of plasma corticosterone concentration. [ABSTRACT FROM AUTHOR]

Aim: Ninjinyoeito (NYT) is a Kampo medicine prescribed for patients with decreased mental and physical energy. Clinical studies demonstrate that NYT ameliorates depressive symptoms in patients with various diseases. However, the underlying therapeutic mechanisms of action remain unclear. The monoaminergic system has been implicated in the neuropathology of depression. Using immobility in the tail suspension test to evaluate depression‐like behavior, we aimed to examine the effects of NYT and the involvement of the α1‐adrenoceptor and serotonin (5‐HT)1A receptor in its mechanism of action. Methods: Immobility in the tail suspension test was used as an index of depression‐like behavior. NYT (1,000 or 2,000 mg/kg/day, once a day for seven days) was orally administered to mice. Prazosin and WAY‐100635 were administered 30 min and 1 h before the test, respectively. Norepinephrine (NE) and 5‐HT levels in the frontal cortex and amygdala were analyzed using a high‐performance liquid chromatography (HPLC) electrochemical detector. Results: NYT (2000 mg/kg/day) shortened the immobility time. Prazosin and WAY‐100635 blocked the NYT‐mediated reduction in immobility time. NYT increased NE levels, but not 5‐HT levels, in the amygdala. Conclusion: NYT reduced immobility time in the tail suspension test, likely by increasing NE levels. The increased NE levels may activate the α1‐adrenoceptor, thereby ameliorating the depression‐like behavior. NYT may therefore improve depressive symptoms in patients by enhancing the noradrenergic system. [ABSTRACT FROM AUTHOR]

Background: Cycloprolylglycine (CPG) is an endogenous dipeptide with a wide range of psychotropic activity and putative therapeutic potential for depression. A small but growing body of data suggests that antidepressant-like effect of CPG is associated with neuroplastic changes in the brain or 5-HT system modulation. However, the mechanisms of the dipeptide action remain elusive. Aims: Here, we characterize the effects of chronic CPG administration on behavior and genes expression of antidepressants sensitive catalepsy (ASC) mice strain, characterized by depressive-like behavior. Methods: ASC mice were injected with saline, fluoxetine (10 mg/kg/day), or CPG (1 and 2 mg/kg/day) during 2 weeks. Behavior was studied using the open field test, novel object test, elevated plus maze test, forced swim test, and tail suspension test (TST). The expressions of genes coding BDNF, CREB, 5-HT1A and 5-HT2A receptors, TPH2, and SERT in the brain were measured with quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Results: Chronic intraperitoneal administration of 1 and 2 mg/kg of CPG revealed the significant antidepressant-like effect by decreasing immobility time in the TST. At the same time, CPG did not negatively affect locomotor activity, cognition, or anxiety. In the real-time quantitative polymerase chain reaction (PCR) assay, chronic CPG treatment (2 mg/kg for 14 days) increased Bdnf mRNA level in the frontal cortex. Conclusions: Our findings extend the evidence for the effectiveness of CPG to reduce depressive-like behaviors. The antidepressant-like effect of CPG is mediated, as least in part, by BDNF-dependent mechanism. The exact mechanism remains to be elucidated, and further studies are warranted. [ABSTRACT FROM AUTHOR]

This research was done to investigate the antidepressant properties of plumbagin using a chronic mild stress induced depression model in experimental animals. Albino mice of either sex were given 3 weeks of chronic mild stress and their antidepressant properties were assessed using the tail suspension test and sucrose preference test. The period of immobility in the tail suspension test and the percentage preference for sucrose solution were both recorded and compared. Plumbagin was given in three doses (4, 8, and 16 mg/kg). The immobility time in the tail suspension test was significantly decreased in the animals that received plumbagin administration during the three phases of the chronic mild stress when compared to control. Further, plumbagin administration dose dependently increased the percentage preference for sucrose solution on par with the standard antidepressant, imipramine. The spontaneous locomotion count was significantly higher in the animals that received a high dose of plumbagin. Further, a high dose of plumbagin significantly reverses the chronic mild stress induced plasma corticosterone and nitrile levels. Additionally, a high level of dopamine was found in the prefrontal and nucleus accumbens parts of the brain. To summarize, plumbagin, in addition to its antioxidant characteristics, has potential antidepressant action at high doses, potentially by raising the dopamine levels. [ABSTRACT FROM AUTHOR]

Objectives: This study investigated the involvement of heme oxygenase-1 (HO-1) in the antidepressant-like effects of ursolic acid (UA), a plant-derived compound with neuroprotective and antidepressant-like properties. Methods: Mice received intracerebroventricular injections of zinc protoporphyrin IX (ZnPP) or cobalt protoporphyrin IX (CoPP) to inhibit or induce HO-1, respectively, together with effective (0.1 mg/kg, p.o.) or sub-effective (0.01 mg/kg, p.o.) doses of UA or fluoxetine (10 mg/kg, p.o.). Immobility time was assessed using the tail suspension test (TST) and the ambulatory behaviour with the open field test. HO-1 immunocontent was evaluated in mice hippocampus and prefrontal cortex. Key findings: ZnPP prevented the anti-immobility effects of UA and fluoxetine. Combined treatment with a sub-effective dose of CoPP and UA synergistically exerted antidepressant-like effects in the TST. Acute administration of UA or CoPP, but not fluoxetine, increased the HO-1 immunocontent in the hippocampus. None of the treatments altered the HO-1 immunocontent in the prefrontal cortex. Conclusions: In conclusion, this work shows that increased hippocampal HO-1 content and activity mediate the antidepressant-like effect of UA in the TST. [ABSTRACT FROM AUTHOR]

Cisplatin therapy is often accompanied by neurotoxicity manifestation, and since the prefrontal cortex is strongly involved in emotion regulation, the aim of this study was to analyze the alterations in the oxidative and apoptotic status of this brain region, with its behavioral impact in rats, following cisplatin administration, with or without N-acetylcysteine supplementation. Thirty-two male Wistar albino rats were randomly divided into four equal experimental groups: control, cisplatin group (single dose of 7.5 mg/kg, intraperitoneally (i.p.), on the fifth day), N-acetylcysteine group (500 mg/kg i.p., on the first and the fifth day), cisplatin + N-acetylcysteine group. Behavioral testing was performed in the tail suspension test. Oxidative stress and apoptotic markers were determined in the prefrontal cortex tissue samples. Cisplatin administration increased lipid peroxidation and decreased the activity of antioxidant enzymes in the prefrontal cortex. Also, cisplatin induced increase in Bax and decrease in Bcl-2 relative gene expression. Simultaneous application of Nacetylcysteine diminished cisplatin-induced alterations in oxidative stress and apoptotic markers. The results obtained in the tail suspension test that nominally resembles antidepressant action of cisplatin (attenuated by N-acetylcysteine), should be attributed to strong motor expression of anxiogenic response to cisplatin (also reversed by Nacetylcysteine). The antioxidant supplementation with NAC diminished cisplatin-induced oxidative damage and pro-apoptotic action in the prefrontal cortex, and significantly influenced specific behavioral alterations. [ABSTRACT FROM AUTHOR]

In order to evaluate the effects of Satureja hortensis L. extract on cisplatin-induced behavioral alterations in the tail suspension test (TST), we included 35 male Wistar albino rats in this study, divided into 7 equal groups. Cisplatin was administered (single dose of 7.5 mg/kg, i.p., on the fifth day) alone, and in groups with orally administered (for 10 days) Satureja hortensis L. extract (50, 100, and 200 mg/kg), and silymarin (100 mg/kg) in individual groups. The behavioral testing was performed in TST, and the following parameters were obtained: the latency to the first immobility, the number of immobility episodes, and the total duration of immobility. Cisplatin application increased the latency to the first immobility, but decreased the number of immobility episodes and the total duration of immobility. Oral administration of Satureja hortensis L. extract in a dose of 100 mg/kg attenuated cisplatin-induced alterations, and those effects were similar to silymarin group. The extract in a dose of 200 mg/kg diminished cisplatin-induced effect only for the total duration of immobility, while in a dose of 50 mg/kg, the extract had no impact on cisplatin effects. Although common use of this methodology would lead to a conclusion that cisplatin produced antidepressant effect, comparison with certain literature data allows the conclusion that this action of cisplatin may be attributed to its anxiogenic action that was attenuated by antioxidant supplementation (Satureja hortensis L.) in an adequate dose (100 mg/kg). [ABSTRACT FROM AUTHOR]

Hypothyroidism causes somatic, psychosocial and affective psychosis, including depression-like behaviors. In this study, (hypothyroidism group; HP group) adult male Sprague Dawley (SD) rats were induced to hypothyroidism after 5 weeks of exposure to 0.05% propylthiouracil (PTU) in potable water, control animals (CON group) were given the same amount of water. The following behavioral experiments were conducted, respectively: open-field test (OFT), forced swimming test (FST), tail suspension test (TST). TT 3 and TT 4 levels were measured after the behavior tests and the expression levels of 5-HT 2 A receptor and 5-HT 2 A receptor proteins were analyzed in the hippocampus and prefrontal cortex. The level of TT 3 and TT 4 in the HP group rats was much lower than that in the CON group. The hypothyroid rats also showed weight loss, much longer immobility time in tail suspension test and forced swimming test. Besides, 5 weeks of PTU administration was associated with significantly decreased expression levels of 5-HT 2 A receptor and 5-HT 2 A receptor proteins compared with control group, which were significantly negatively correlated with immobility time in FST and TST. In conclusion, our results suggest that hypothyroidism induces depressive behaviors through the influence of the serotonin system, and the decreased expression of the 5-HT 2 A receptor is an important cause of the depressive behaviors in hypothyroidism. [ABSTRACT FROM AUTHOR]

Rodent models of depression are useful for the investigation of cellular and neuronal mechanisms of antidepressant drugs and for the discovery of potential new targets. In this study, we examined the antidepressant‐like effect of scopolamine, a non‐selective muscarinic antagonist, in a genetic mouse model of depression obtained through a selective breeding strategy and called H/Rouen. In this model, we observed that scopolamine was active both in males and females at a lower dose (0.03 mg/kg) in the tail suspension test, 30 min following its administration, than observed in CD‐1 mice. In addition, we showed this antidepressant‐like effect was partly inhibited by an injection of 10 mg/kg of the AMPA receptor antagonist NBQX in both males and females, suggesting the antidepressant‐like effect of scopolamine was mainly driven by AMPA receptors in the H/Rouen mouse line. Altogether, our results showed the high sensitivity of the H/Rouen mouse model of depression to study the antidepressant‐like effects of pharmacological compounds. [ABSTRACT FROM AUTHOR]

[Display omitted] • A new series of oxadiazole clubbed benzhydrylpiperazines (AP1-12) was designed, synthesized and evaluated for MAO inhibitory potential. • In this series, compounds AP3 and AP12 displayed most potent, selective and reversible inhibition of MAO-A enzyme. • In FST and TST studies, AP3 and AP12 exhibited potential antidepressant-like behaviour similar to standard drug fluoxetine. • Both potent compounds displayed good binding affinity and stability at binding pocket of MAO-A in in silico studies. Arylpiperazine clubbed various heterocyclic molecules present potential pharmacophoric structural features for the development of psychoactive drugs. There are various CNS active molecules possessing arylpiperazine moiety in their pharmacophore approved by USFDA. In the current study, we have explored the benzhydrylpiperazine moiety clubbed with various substituted oxadiazole moieties (AP1-12) for their monoamine oxidase (MAO) inhibition and antidepressant potential. Compounds AP3 and AP12 exhibited highly potent and selective MAO-A inhibition with IC 50 values of 1.34 ± 0.93 µM and 1.13 ± 0.54 µM, respectively, and a selectivity index of 10- and 13-folds, respectively. Both the compounds displayed reversible binding character at the active site of MAO-A. In further in vivo evaluation, both the compounds AP3 and AP12 displayed potential antidepressant-like character in FST and TST studies via significantly reduced immobility time in comparison to non-treated animals. These compounds displayed no cytotoxicity in SH-SY5Y cell lines, which indicates that these compounds are safe for further evaluation. In silico studies reveal that synthesized compounds possess drug-likeness with minimal to no toxicity. In silico studies were conducted to understand the binding interactions and stability of compounds at the binding pocket of enzyme and observed that both the best compounds fit well at the active site of MAO-A lined by amino acid residues Tyr69, Asn181, Phe208, Ile335, Leu337, Phe352, and Tyr444 similar to standard MAO-A inhibitor clorgiline. The molecular dynamic studies demonstrated that AP3 and AP12 formed quite a stable complex at the active site of MAO-A and did not break under small abruption forces. The favourable binding interactions and appropriate ADMET properties present the benzhydrylpiperazine clubbed oxadiazole pharmacophoric features as a potential structural skeleton for further clinical evaluation and development of a new antidepressant drug molecule. [ABSTRACT FROM AUTHOR]

Purpose: Depression is one of the most common psychological disorders. The nutritional etiology of the depression proposes that vitamin D may play a significant role in the pathogenesis of depression. Further, vitamin D deficiency has been found to aggravate depression in animals. Therefore, vitamin D treatment might be a potential therapeutic aid in depression management. This study aimed to explore the antidepressant effects of vitamin D in a Bacillus Calmette-Guerin (BCG)-induced depression model. Methods: Thirty-six mice were randomly assigned to short-term and long-term experimental groups. In each group, mice were randomly subcategorized into three subgroups: 1. control (received vehicle), 2. BCG (received BCG [107 CFU/mouse]), and 3. BCG + vitamin D (received vitamin D [60.000 IU/kg] before BCG [107 CFU/mouse] inoculation). After completion of the two experimental periods (3 days for the short-term group and 2 weeks for the long-term group), the mice underwent three behavioral tests: locomotor activity, the forced swimming test (FST), and the tail suspension test (TST). Results: Locomotor activity did not significantly differ among the subgroups in either the long-term or short-term groups. In the short-term group, the total immobility time on the FST was decreased in the vitamin D-treated group compared to the BCG group. However, in the TST, no significant difference was found between the vitamin D-treated group and the BCG group. In the long-term group, the immobility time on the FST was decreased in the vitamin D-treated group compared to the BCG group. Similarly, the total immobility time on the TST was also significantly lower in the vitamin D-treated mice than in the BCG-treated mice. Conclusion: Vitamin D is useful in the management of depressive behavior. The potential role of vitamin D in the etiology of depression should be investigated in future work. [ABSTRACT FROM AUTHOR]

Phaseolus vulgaris Linn commonly known as red kidney bean, it is enriched in protein, carbohydrates and dietary fibres. Beans have nutritional and health benefits and also possess antimicrobial, antihyperglycemic, antioxidant and anticancer activity due to presence of bio-active chemical constituents. The following study was carried out to evaluate the anti-depressant activity of Phaseolus vulgaris fixed oil (PVFO) using forced swim test and tail suspension test in mice. In this study animals assigned into four groups (n=7). Group I: Control normal saline (2 mL/Kg), Group II: PVFO I (2 mL/Kg), Group III: PVFO II (4 mL/Kg) and Group IV: standard amitriptyline (10 mg/Kg). The results were significant and indicated the possible anti-depressant role of Phaseolus vulgaris fixed oil. [ABSTRACT FROM AUTHOR]

Depressive symptoms are throughout our life, especially in the older population, the sex hormones reduction link to a high risk of depression. In this study, we investigated whether bilateral orchiectomy (ORX) modifies mice behaviors and antidepressant drugs effects through tail suspension test (TST). We evaluated behavioral changes at 1 week, 2 weeks, 1 month, and up to 2 months after ORX. The behavior responses to doxepin, fluoxetine, and venlafaxine at 1 week, 2 weeks, 1 month, and 2 months after ORX were evaluated. No apparent difference was detected among the durations of immobility of the control group, sham operation group, and ORX group in the TST at 1 week and 2 weeks after ORX. But the immobility time of ORX group was obvious longer than that of both control group and sham operation group at 1 month and 2 months after ORX. Only the antidepressant effect of venlafaxine was observed at 1 week and 2 weeks after ORX, while the antidepressant response to fluoxetine decreased 1 month and 2 months after ORX. The response to antidepressant drugs was strongly modified in ORX mice. Our results suggest that not all antidepressant drugs are suitable for depression with androgen deficiency.HighlightsMice with low androgen were more prone to depression-like behaviors.The response to antidepressants changed under the condition of low androgen in mice.Not all antidepressant drugs are appropriate for patients with low androgen. [ABSTRACT FROM AUTHOR]

Background: Our previous studies showed that xanthone derivatives with N -(2-methoxyphenyl)piperazine fragment have an affinity to the 5-HT1A receptor and show antidepressant-like properties in rodents. In this study, we tested three xanthone derivatives, HBK-1 (R, S) and its enantiomers, in which we increased the distance between the piperazine and xanthone fragments by using a hydroxypropoxy linker. We hypothesized that this would increase the binding to the 5-HT1A receptor and consequently, pharmacological activity. Aims: We aimed to assess the in vitro and in vivo pharmacological activity of the xanthone derivatives. Methods: We evaluated the in vitro affinity for serotonin 5-HT1A and 5-HT2A receptors and serotonin transporter. We also determined the intrinsic activity at the 5-HT1A receptor. We investigated the antidepressant-like properties and safety after acute administration (dose range: 1.25–20 mg/kg) using the forced swim, tail suspension, locomotor activity, rotarod and chimney tests in mice. We also evaluated the basic pharmacokinetic parameters. Results: Our results indicated that the compounds showed a high affinity for the 5-HT1A receptor but very weak antagonistic properties in the Ca2+ mobilization assay; however, they showed significant agonistic properties in the β-arrestin recruitment assay. In both behavioural tests the studied xanthone derivatives showed antidepressant-like activity. Pre-treatment with p-chlorophenylalanine or WAY-100635 abolished their antidepressant-like activity. None of the compounds caused motor impairments at antidepressant-like doses. The racemate penetrated the blood–brain barrier and had a relatively high bioavailability after intraperitoneal administration. Conclusions: Xanthone derivatives with N -(2-methoxyphenyl)piperazine fragment and hydroxypropoxy linker show increased binding to the 5-HT1A receptor and may represent an attractive putative treatment candidate for depression. [ABSTRACT FROM AUTHOR]

Rationale: Major depressive disorder is a psychiatric disorder that requires considerable attention, since it dramatically impairs the quality of life of the sufferers. The available treatments do not have the efficacy needed, often presenting several side effects. Organoselenium compounds and benzamides have presented some pharmacological properties, among them an antidepressant-like effect. Objectives and methods: This study evaluated the antidepressant-like effect of N-(3-(phenylselanyl)prop-2-yn-1-yl)benzamide (SePB), an organoselenium compound containing a benzamide moiety, on the forced swimming test (FST) and the tail suspension test (TST) in mice, as well as the involvement of the serotonergic system in its effect. Results: SePB, tested after different times (15–120 min) and doses (1–50 mg/kg, intragastrically (i.g.)), reduced immobility of male mice during FST and TST, without changing locomotor activity in the open-field test (OFT), demonstrating its antidepressant-like effect. SePB (10 mg/kg) also produced an antidepressant-like effect in female mice in the TST. The preadministration of the serotonin (5-HT) depletor p-chlorophenylalanine (pCPA; 100 mg/kg, intraperitoneal route (i.p.) once daily for 4 days) prevented the anti-immobility effect of SePB, indicating that the serotonergic system is involved in the SePB antidepressant-like effect. The preadministration of the selective serotonergic receptor antagonists WAY100635 (0.1 mg/kg, subcutaneous route (s.c.), a selective 5-HT1A receptor antagonist), ketanserin (1 mg/kg, i.p., a 5-HT2A/2C receptor antagonist), and ondansetron (1 mg/kg, i.p., a selective 5-HT3 receptor antagonist) also prevented the anti-immobility effect of SePB, demonstrating that these receptors are involved in the antidepressant-like effect of SePB. Conclusion: The search for new antidepressants drugs is a noteworthy goal. This study has described a new compound with an antidepressant-like effect, whose mechanism of action is related to modulation of the serotonergic system. [ABSTRACT FROM AUTHOR]

Psychoneuroimmunological studies have clearly demonstrated that both cellular and humoral immunity are related to major depression. Soluble ST2 is regarded as a key molecule regulating immune system as well as cell proliferation. Indeed, soluble ST2 is reported to reduce IL-33-induced IL-6 and TNF-α production in macrophages and IL-33-induced IL-5 and IL-13 production in type 2 innate lymphoid cells. Elevated serum concentrations of soluble ST2 have been reported in patients with neuropsychiatric disorders, suggesting pathophysiological roles of soluble ST2 in behavioral phenotypes. Nevertheless, the relation between soluble ST2 and depressive behavior remain to be uncovered. To complement this point, we performed broad behavioral phenotyping, utilizing transgenic mice with a high concentration of serum ST2 in the present study. Soluble ST2 overexpression mice (ST2 Tg mice) were generated on a C3H/HeJ background. ST2 Tg mice crossed onto the BALB/c genetic background were used. Before starting tests, each mouse was observed in a clean cage for a general health check and neurological screening tests. In Experiment I, comprehensive behavioral phenotyping was performed to reveal the role of soluble ST2 on sensorimotor functions, anxiety-like behaviors, depression-like behaviors, social behaviors, and learning and memory functions. In Experiment II, to confirm the role of soluble ST2 on depression-like behaviors, a depression test battery (two bottle choice test, forced swimming test, and tail suspension test) was applied. The general health check indicated good general health and normal gross appearance for ST2 Tg mice. Further, the neurological reflexes of all the mice were normal. We found that soluble ST2 overexpression resulted in decreased social interaction. Moreover, depression-like behaviors of ST2 Tg mice were observed in two well-established behavioral paradigms, the forced swimming test and the tail suspension test. Nevertheless, hedonic reaction to sucrose was observed in ST2 Tg mice similar to WT mice. These results suggest the depression in the ST2 Tg mice. In conclusion, through a series of experiments, we established the animal model for assessing role of soluble ST2 in neuropsychiatric disorders, and revealed the possible involvement of soluble ST2 in depressive behavior. [ABSTRACT FROM AUTHOR]

Background: Depression is a mental disorder characterized by low mood and loss of pleasure or interest in usual activities and often results in cognitive dysfunction such as impairment of learning and memory. For most of the synthetic antidepressants, severe defects such as narrow spectrum, adverse reactions, high drug price, and easy recurrence exist. Barley is one of the richest sources of antioxidants; therefore, we examined whether barley has an effect on depression, learning, and memory in a mouse model of reserpine-induced depression. Methods: Mice were individually acclimated for 1 week and then treated with barley (200 mg/kg, p. o.) or/and fluoxetine (20 mg/kg, i. p.) for 4 weeks prior to reserpine treatment. Mice were then injected with a single dose of reserpine (2 mg/kg, i. p.) or vehicle (20 mg/kg, i. p.) and assessed for mouse behaviors 1 h prior to tests. Mouse behavior was examined in the forced swimming test, tail suspension test, hole-board test, novel place/object recognition, social interaction test, spontaneous locomotor movement (SLMA), and stereotype movement following completion of the treatment protocol. Results: There was a significant antidepressant-like effect in the forced swimming test among the barley group than in the reserpine-treated group, and these decreases were significantly attenuated to a similar extent by treatment with fluoxetine. The effect of barley on the mean duration of immobility time was significantly attenuated in comparison with the reserpine group (P < 0.05). Moreover, the number of head pokes was significantly increased in the barley group in comparison with the reserpine or fluoxetine group. The mean duration of immobility time in the tail suspension test was significantly reduced in mice in the barley group in comparison with the reserpine group (P < 0.05). Furthermore, the social behavior test indicated that mice treated with fluoxetine have a significant increase in the distance covered by the mice toward familiar ones compared to the barley group, whereas the distance measured to the stranger mice was significantly increased among those who received fluoxetine with barley in comparison with the barley group alone. Finally, novel object recognition test, spontaneous locomotor movements (SLMA), and the stereotype movements showed that barley significantly decreased time spent on exploring the novel objects as well as in stereotype movements in comparison with the reserpine group. Conclusion: We conclude that barley can ameliorate depressive-like effects. Taken together, these findings demonstrate that barley may be effective in treating patients with depression. [ABSTRACT FROM AUTHOR]

[Display omitted] • SePB presented antidepressant-like effect in tail suspension test in mice. • A 5-HT 4 receptor antagonist prevented the antidepressant-like effect of SePB. • In silico analysis evidenced a high affinity between 5-HT 4 receptors and SePB. • SePB is a promising compound for the development of novel treatments for MDD. The serotonin type 4 receptor (5-HT 4 R) shows promise as a target for treating major depressive disorder (MDD). Studies have demonstrated that 5-HT 4 R agonists have a faster antidepressant-like effect compared to conventional medications. Developing drugs that modulate this receptor could lead to faster and more effective MDD treatments. The compound N -(3-(phenylselanyl)prop-2-yn-1-yl)benzamide (SePB) induces an antidepressant-like effect in mice. The present study explored if the 5-HT 4 R mediates SePB's antidepressant effect. For this, male Swiss mice were treated with GR113808 (0.1 mg/kg, intraperitoneally – i.p.), a 5-HT 4 R antagonist, and SePB (10 mg/kg, intragastrically – i.g), and then subjected to the tail-suspension test (TST) and open-field test (OFT). In silico tests were conducted to analyze SePB's binding affinity to the 5-HT 4 R and identify participating amino acid residues. The administration of GR113808 blocked the antidepressant-like effect of SePB in the TST without changing locomotor activity in the OFT. Moreover, SePB exhibited a high binding affinity between the 5-HT 4 R (−7.9 kcal/mol) and the amino acid residues Leu298, Asp100, Thr97, Arg96, Glu80, Leu81, Cys184, Val185, and Phe186 seem to be important for this interaction. The involvement of the 5-HT 4 R in the antidepressant-like effect of SePB suggests potential for novel therapies in MDD. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a debilitating illness that affects millions of people worldwide. Currently available antidepressants often take weeks to months to reach their full effect, which leads to an increased risk of suicidal behavior in patients with MMD. Intranasally, esketamine has emerged as an alternative to current antidepressants because of its rapid onset and long-lasting effects in patients with MDD. Animal models are useful for the initial pharmacological screening and for a better understanding of the mechanisms underlying the effects of new drugs with potential against MDD. There is a lack of data on alternative routes of drug administration, either oral or injectable, that can be used in preclinical studies. This study aimed to test whether ketamine has antidepressant-like effects in mice when administered via nebulization using a low-cost apparatus. When mice whose depressive-like behavior was induced by corticosterone were treated with nebulized ketamine at concentrations of 1.3, 2.6, and 5.2 mg/mL, immobility was reduced by 38.6 %, 62.0 %, and 61.1 %, respectively, in the forced swimming test (FST) and 43.6 %, 42.1 %, and 57.9 %, respectively, in the tail suspension test (TST). When depression-like behavior was induced by dexamethasone, nebulization with ketamine reduced immobility by 79.7 %, 49.2 %, and 44.4 % in the FST and 80.9 %, 71.4 %, and 80.4 %, respectively, in the TST. When depression-like behavior was induced by the association between dexamethasone and unpredictable chronic mild stress (UCMS) exposure, immobility was reduced by 26.1 %, 55.3 %, and 19.1 % in FST. Mice treated with nebulized ketamine did not show significant changes in the distance covered or in the time spent moving in the open field test. The efficacy of intraperitoneal and nebulized ketamine is equivalent, which shows that nebulization can be an alternative inexpensive route of drug administration for behavioral studies in rodents. • Nebulized ketamine reduces the immobility of mice in the FST and TST. • Nebulized ketamine is as effective or more effective than intraperitoneal administration. • Nebulized ketamine has a specific antidepressant-like effect that is unrelated to changes in animal mobility. • The nebulization of antidepressant drugs may be an alternative to preclinical studies. [ABSTRACT FROM AUTHOR]

The circadian system regulates sleep/wake cycles, metabolism, mood, and other functions. It also influences medication efficacy. In this study, we studied the chronopharmacological profiles of antidepressants with various modes of action. We also investigated the effects of dosing time on the pharmacological activity of several antidepressants acting on serotonergic, noradrenergic, and/or dopaminergic neurons. C57BL/6 mice were intraperitoneally administered fluoxetine, imipramine, venlafaxine, or bupropion at 08:00 h (morning), 14:00 h (mid-day), 20:00 h (evening), or 02:00 h (mid-night). Antidepressant activity was evaluated by the tail suspension test. All antidepressants reduced immobility, and their activities varied according to the dosing time. Fluoxetine and imipramine induced relatively strong rhythms with high amplitudes. Their maximal effects were observed in the morning and evening, respectively. Venlafaxine and bupropion induced weak rhythms with maximal effects in the evening and dawn, respectively. These results suggest that the antidepressant activity is associated with circadian fluctuation, and antidepressants with different modes of action have different chronopharmacological profiles. They affect locomotor activity in animals placed in novel (unfamiliar) environments. Fluoxetine, imipramine, and venlafaxine reduced locomotor activity, whereas bupropion increased it. The effects on locomotor activity also vary with circadian rhythm, and the tested drugs showed a maximal effect during the light phase. The peak time was different from that in TST. Plasma and brain levels of all drugs were slightly higher in the morning than in the evening. The dosing time dependency of the antidepressant activity did not correlate with the sedative/stimulatory activity or tissue drug level. Therefore, these latter two factors may have only a small impact on circadian antidepressant activity fluctuations. The relative activity of the serotonergic, noradrenergic, and dopaminergic systems may determine the chronopharmacological profiles of each drug. These results suggest the possibility that drug therapy be optimized by considering the dosing time when the antidepressant activity is high and other pharmacological activities leading to adverse effects are low. Further studies using animal models of depression and in clinical settings are necessary to confirm the effects of dosing time on depressed subjects. [ABSTRACT FROM AUTHOR]

The aim of this investigation was to evaluate the antidepressant activity of the ethanolic extracts of "toronjil azul"(Dracocephalum moldavica L.). Methodology: The forced swimming test (FST) and tail suspension test (TST) were performed on CD-1 mice to evaluate the antidepressant activity of the ethanolic extracts. The ethanolic extracts were administered orally at an 80 and 100 mg/kg. The animals were dosed 1, 6 and 24 h before initiating the FST assay and 40 minutes before for the TST assay. Imipramine and fluoxetine were dosed at 15 mg/kg, while the flavonoid quercetin was given an a lower concentration of 10 mg/kg as a positive controls. Results: The extracts of Dracocephalum moldavica L. and significantly decreased the immobility time in the FST and TST assays when compared with the negative control and reported similar values than those obtained with the positive controls. Conclusion: The results obtained indicate that extract of Dracocephalum moldavica L. have antidepressant effect similar to those obtained by. [ABSTRACT FROM AUTHOR]

The aim of the present work was to evaluate the anti-oxidant and anti-depressant potentials of the ethanolic bark extract of Annona muricata. Ethanolic bark extracts of Annona muricata was subjected to preliminary and quantitative phytochemical screening. In vitro Anti-oxidant activity of Annona muricata was performed using phosphomolybdenum assay with Ascorbic acid as the standard. As the extract exhibited potent anti-oxidant activity, it was investigated further for its anti-depressant activity using Forced swim test(FST), tail suspension test(TST), Digital photoactometer test (DPT) and Open field test(OFT). Imipramine & Fluoxetine [10mg/kg] were used as reference drugs for the anti-depressant experiments. ethanolic bark extract of Annona muricata exhibited significant anti-oxidant activity with significant increase of absorbance in a concentration dependent manner while in anti-depressant activity there was considerable decrease in the immobility time. Altogether, these results suggest that the ethanolic bark extract of Annona muricata could be used as a potential anti-oxidant and anti-depressant agent. [ABSTRACT FROM AUTHOR]

• Oleamide potentiates activity of conventional antidepressant drugs. • AM251 enhances activity of conventional antidepressant drugs. • Interplay between CB 1 receptor ligands and antidepressants is pharmacodynamic in nature. Antidepressants that target the monoaminergic system are prescribed most frequently in the psychiatric practice. However, not all patients benefit from their use. It is generally known that co-administration of agents aiming distinct targets may increase the therapeutic effect and at the same time permit dose reduction. A number of studies have suggested a CB 1 receptor-mediated interplay between the endocannabinoid system and the monoaminergic signalling in the brain. Therefore, we wanted to determine whether the CB 1 receptor ligands (oleamide and AM251) affect the activity of the common antidepressant drugs that influence the monoaminergic system. In order to determine the antidepressant‐like activity, the forced swim test and the tail suspension test in mice were used. Additionally, brain concentrations of the tested antidepressants were evaluated by the HPLC method. Concurrent intraperitoneal administration of per se inactive doses of oleamide (5 mg/kg) or AM251 (0.25 mg/kg) and imipramine (15 mg/kg), escitalopram (2 mg/kg), and reboxetine (2.5 mg/kg) reduced the immobility time of animals in the forced swim test and the tail suspension test. The observed effect was not associated with hyperlocomotion of animals. Summarizing, the outcomes of the present study demonstrated that modulation (i.e., activation or inhibition) of the CB 1 receptor function potentiates the antidepressant activity of common drugs that influence the monoaminergic (serotonergic and noradrenergic) system. This effect is most probably predominantly pharmacodynamic in nature instead of pharmacokinetic. [ABSTRACT FROM AUTHOR]

Solanum surattense Burm. f. is used in traditional medicine for various health problems, including depression. This research was conducted to explore the antidepressant effect of Solanum surattense in order to validate its therapeutic use in depression. Forced swim test (FST), tail suspension test (TST) and open field test models of mice were used for the investigation of antidepressant effect of Solanum surattense crude extract (Ss.Cr) by the determination of behavioural responses of mice like swimming, climbing, immobility time, ambulations and rearings in these test models. Ss.Cr tested positive for alkaloids, flavonoids, saponins, steriods and tannins. It exhibited antidepressant effect by dose dependently (100-200 mg/Kg) decreasing immobility time (P < 0.001 vs normal saline respectively) in both FST and TST, while increased swimming duration (P < 0.01, P < 0.001 vs normal saline respectively), as exhibited by fluoxetine (20 mg/Kg). Ss.Cr did not significantly alter ambulation and rearing frequencies in open field test. SS.Cr did not produce any mortality up to 5 g/Kg dose in acute toxicity test. These results indicate that Solanum surattense possess antidepressant activity. The presence of phytochemicals, such as flavonoids and saponins argue the cogency of the proclaimed folk medicinal effect in depression. [ABSTRACT FROM AUTHOR]

The present study deals with validation of adaptogenic potential of different extracts (petroleum ether, dichloromethane, chloroform, ethanol and aqueous) of an Ashtavarga plant, Polygonatum cirrhifolium (Wall.) Royle by in vitro , in vivo and in silico studies. In vitro adaptogenic potential was determined by evaluating in vitro antioxidant activity using ABTS, DPPH, and total antioxidant capacity assays. Anoxia stress tolerance (AST), forced swimming endurance test (FST), tail suspension test (TST) and chronic cold restraint stress (CCRS), models have been used for in vivo adaptogenic study. Docking study of selected chemical constituents (from GC/MS analysis of different extracts) with glucocorticoid protein (PDB 5NFP) and c-Jun N-terminal kinase 3 protein (PDB 2P33) was carried out for analyzing in silico adaptogenic activity. Ethanol extract showed highest antioxidant power among all the extracts. Swimming time in FST and tolerance time in AST increased significantly by petroleum ether (PE) and ethanol (EE) extract treatment compared to stress control animals. PE and EE treatment significantly reduced the immobility time in TST over stress control animals. Further, pre-treatment with PE and EE significantly decreased the stress induced elevated levels of various biochemical parameters such as blood glucose, total protein, triglycerides, corticosterone and blood urea nitrogen. Docking study revealed good interaction of sitosterol with PDB 5NFP (docking score of 7.66 kcal/mol). 3,5-Dicyclohexyl-4-hydroxy-benzoic acid-methyl ester and 6,7-Dichloro-5-[(1-ethylpyrrolidin-2-yl)methylami-no]-1,3-dimethyl-pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione showed excellent interaction with PDB 2P33. On the basis of the present findings, it can be perceived that P. cirrhifolium possessed noteworthy adaptogenic activities which might be due to antioxidant property of different secondary metabolites of the plant. • Successive extracts of Polygonatum cirrhifolium with solvents of different polarity have been prepared using soxhlet apparatus. • Total phenolic, flavonoid and tannin contents of different extracts were analyzed. • GC/MS analysis of various extracts confirmed presence of a number of chemical constituents. • Extracts exhibited promising free radical scavenging activities. • The extracts showed adaptogenic activity and controlled stress-induced elevated levels of various biochemical parameters. • Molecular docking studies of few compounds demonstrated good interaction with 5NFP and 2P33 receptors. [ABSTRACT FROM AUTHOR]

Research in the metal oxide nanoparticles and nanotechnology field is growing. Zinc oxide (ZnO) nanoparticles (NPs) have been widely used in the various products and industries. Regarding the probable toxicity of ZnO NPs on central nervous system (neurotoxicity), the current study was designed to investigate the effects of maternal exposure to ZnO NPs during pregnancy on depressive-like behaviors in mice offspring, using two validated animal models of depression. Thirty pregnant female mice were distributed into three groups (n = 10 for each group). The two experimental groups were injected subcutaneously at gestation day 5, 8, 11, 14, and 17 with 100 µl of ZnO NPs solution at doses of 0.5 and 1 mg/ml, respectively. The control group was treated with a similar subcutaneous injection of saline containing 0.05% Tween-80 as vehicle. Neurobehavioral tests including forced swimming test (FST) and tail suspension test (TST) were used to evaluate depressive-like behaviors in 3-week-old and 6-week-old male and female offspring (n = 10/group). The results of this study indicated that subcutaneous injection of ZnO NPs at 0.5 and 1 mg/ml dose dependently increased the immobility time in 3-week-old and 6-week-old mice in both the FST and TST (P < 0.05). Moreover, increasing age also significantly increased the duration of immobility in both the FST and TST (P < 0.05). In addition, sex differences were observed in behavioral responses, such as female mice were more immobile than male mice in both the FST and TST (P < 0.05). In conclusion, these findings demonstrated that the depressive-like effects of ZnO NPs may be due to its neurotoxic influences during neuronal development. [ABSTRACT FROM AUTHOR]

Unsatisfactory therapeutic effects of currently used antidepressants force to search for new pharmacological treatment strategies. Recent research points to the relationship between depressive disorders and the adenosinergic system. Therefore, the main goal of our studies was to evaluate the effects of DMPX (3 mg/kg, i.p.), which possesses selectivity for adenosine A2A receptors versus A1 receptors, on the activity of imipramine (15 mg/kg, i.p.), escitalopram (2.5 mg/kg, i.p.), and reboxetine (2 mg/kg, i.p.) given in subtherapeutic doses. The studies carried out using the forced swim and tail suspension tests in mice showed that DMPX at a dose of 6 and 12 mg/kg exerts antidepressant-like effect and does not affect the locomotor activity. Co-administration of DMPX at a dose of 3 mg/kg with the studied antidepressant drugs caused the reduction of immobility time in both behavioral tests. The observed effect was not associated with an increase in the locomotor activity. To evaluate whether the observed effects were due to a pharmacokinetic/pharmacodynamic interaction, the levels of the antidepressants in blood and brain were measured using high-performance liquid chromatography. It can be assumed that the interaction between DMPX and imipramine was exclusively pharmacodynamic in nature, whereas an increased antidepressant activity of escitalopram and reboxetine was at least partly related to its pharmacokinetic interaction with DMPX. [ABSTRACT FROM AUTHOR]

[Display omitted] 7-substituted tetrahydroisoquinolines derivatives were designed, synthesized, and evaluated for neuroprotective properties. We summarized the preliminary structure activity relationships (SAR). Compound 3i was screened as a hit compound and its antidepressant activity was evaluated by employing the forced swimming test, tail suspension test. Additionally, ADMET profile (absorption, distribution, metabolism, excretion and toxicity properties) of the compound 3i was predicted in order to evaluate their lead-like properties and safety. The interaction of compound 3i bound to MAO-A was explored using molecular docking and molecular dynamics simulation. Results of biological studies revealed that the compound 3i exhibited almost equal antidepressant activity compared with magnoflorine. Compound 3i is predicted to possess good drug like properties and safety based on ADMET profile predictions. This work provides ideas for the drugs discovery of antidepressant agents. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Many of the currently available antidepressants have serious adverse effects and are also expensive. Traditional medicines are major sources of original drugs, and their role in effective treatment is remarkable. In Turkish folk medicine, decoctions and infusions are prepared from the flowers of Anthemis wiedemanniana Fisch. & Mey. They exert antispasmodic and sedative effects and are also used for treating urinary inflammations. The present study was designed to evaluate the antidepressant activity of A. wiedemanniana , which is used against central nervous system disorders in Turkish folk medicine. Materials and methods n -Hexane, ethyl acetate, and methanol (MeOH) extracts were prepared from the flowers of the plant. The antidepressant potentials of these extracts were evaluated in mouse models using the forced swimming test, tail suspension test, and antagonism of tetrabenazine-induced ptosis, hypothermia, and suppression of locomotor activity. The results were compared with those in control and reference groups, and active constituents of the plant were determined. The MeOH extract of A. wiedemanniana was subjected to various chromatographic separation techniques, leading to the isolation and identification of the active component(s). Results After confirmation of the antidepressant activity, the MeOH extract was subjected to successive solvent partitioning using solvents of increasing polarity, yielding four subextracts. Each subextract was tested on the same biological activity models. Fraction B was found to have the highest activity and subjected to further chromatographic separation. Isolated germacronolide-type sesquiterpene lactones were elucidated as tatridin A (1) and tanachin (1-epi-tatridin B) (2) , which were responsible for the antidepressant activity of the flowers. Conclusions This study explored the antidepressant potential of A. wiedemanniana. Using bioassay-guided fractionation and isolation techniques, tatridin A and tanachin (1-epi-tatridin B) were determined as the main active components of the flowers. Further antidepressant mechanistic studies should be conducted for exploring the activity of these compounds against depression. This study can be an important step in the discovery of newer antidepressants. [ABSTRACT FROM AUTHOR]

Abstract Improved understanding of how depression and social isolation interact to increase cardiac morbidity and mortality will improve public health. This experiment evaluated the effect of pharmacological autonomic blockade on cardiac and behavioral reactivity following social isolation in prairie voles. Experiment 1 validated the dose and time course of pharmacological autonomic antagonism of peripheral β-adrenergic (atenolol) and muscarinic cholinergic receptors (atropine methyl nitrate), and Experiment 2 used a novel protocol to investigate behavioral responses in the tail suspension test during pharmacological autonomic blockade as a function of social isolation (vs. paired control). Prairie voles isolated for 4 weeks (vs. paired) displayed significantly elevated heart rate and reduced heart rate variability. Autonomic receptor antagonism by atenolol led to exaggerated reductions in heart rate and standard deviation of normal-to-normal intervals, and lower amplitude of respiratory sinus arrhythmia in the isolated group (vs. paired). Administration of atropine led to an attenuated increase in heart rate in the isolated group (vs. paired), and similar near-zero levels of respiratory sinus arrhythmia amplitude in both groups. During the tail suspension test, isolated animals (vs. paired) displayed significantly greater immobility. In paired animals, atenolol administration did not influence immobility; atropine administration increased the duration of immobility (vs. vehicle). In isolated animals, atenolol administration increased the duration of immobility; atropine did not influence immobility duration (vs. vehicle). The current study contributes to our understanding of differential effects of social isolation and autonomic imbalance on cardiac and behavioral reactivity. Highlights • Depression and social isolation interact to influence cardiac function. • Animal models are a useful tool to study these interactions. • Autonomic function and behavior were studied in a novel paradigm in prairie voles. • Both social isolation and autonomic imbalance contribute to depression. [ABSTRACT FROM AUTHOR]

Abstract Scopolamine, a muscarinic cholinergic receptor antagonist, exerts fast and prolonged antidepressant effects in the clinic. In contrast, the current treatments for major depressive disorder (MDD) require long-term drug administration. On the other hand, the sole use of scopolamine might be related to the high risk of adverse effects. Therefore, it may be preferable to reduce its therapeutic dose. A new approach might include the co-administration of low-dose scopolamine with selected ligands of metabotropic glutamate (mGlu) receptors, which are known to possess antidepressant-like activity in several rodent tests and models of depression. The aim of the present study was to evaluate the potential antidepressant activity of low-dose scopolamine combined with an allosteric agonist of mGlu7 receptors, AMN082 in C57BL/6 mice. It was found that the combination of scopolamine (0.1 mg/kg) and AMN082 (1 mg/kg) exerted significant antidepressant-like effects in the tail suspension test (TST), but these effects were not observed in the mGlu7−/− mice. Furthermore, low-dose AMN082 co-administered with low-doses scopolamine (0.03 and 0.1 mg/kg) induced antidepressant-like activity in the forced swim test (FST) in mice. The tested compounds did not affect locomotor activity and did not impair spatial memory in the Morris water maze (MWM) test or motor coordination in the rotarod test. The results strongly indicated that there is an enhanced antidepressant-like action of scopolamine by AMN082. Co-administration of scopolamine with AMN082 might be a new strategy with better efficacy and a lower risk of adverse effects compared with the sole use of scopolamine or AMN082. Highlights • AMN082 enhances the antidepressant-like effect of scopolamine in the TST and the FST in mice. • mGlu7 receptor is crucial in the antidepressant-like effect of jointly given scopolamine and AMN082. • Combined administration of scopolamine and AMN082 does not impair spatial memory in the Morris water maze. [ABSTRACT FROM AUTHOR]

Objectives: The present study aims to assess the antidepressant activity of Ixora coccinea extracts in mice and phytochemical analysis of the active extract by GC-MS. Materials and Methods: After oral administration of extracts, tail suspension test (TST), force swim tests (FST), and open field tests (OFT) were performed to assess the antidepressant activity. GC-MS analysis of methanol extract of I. coccinea was performed to ascertain the chemical constituents in the bioactive extract. Results: The methanol extract of I. coccinea at dose of 100 and 200 mg/kg body weight, p.o. significantly reduced the total duration of immobility in the TST as well as FST (p<0.01). I. coccinea extracts showed no significant changes in locomotor activity in OFT. Conclusion: The methanol extract of I. coccinea possesses antidepressant-like properties in mice with no significant effect on locomotor activity in OFT. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Recent studies imply that glial activation plays a role in the pathogenesis of psychiatric disorders, such as schizophrenia and major depression. We previously demonstrated that Gunn rats with hyperbilirubinemia show congenital gliosis and schizophrenia‐like behavior. Methods: As it has been suggested that major depression involves glial activation associated with neuroinflammation, we examined whether Gunn rats show depression‐like behavior using the forced swimming test (FST) and the tail suspension test (TST). In addition, we quantitatively evaluated both microgliosis and astrogliosis in the hippocampus of Gunn rats using immunohistochemistry analysis of the microglial marker ionized calcium‐binding adaptor molecule (Iba) 1 and the astrocytic marker S100B. Results: Both the FST and TST showed that immobility time of Gunn rats was significantly longer than that of normal control Wistar rats, indicating that Gunn rats are somewhat helpless, a sign of depression‐like behavior. In the quantification of immunohistochemical analysis, Iba1immunoreactivity in the dentate gyrus (DG), cornu ammonis (CA) 1, and CA3 and the number of Iba1‐positive cells in the CA1 and CA3 were significantly increased in Gunn rats compared to Wistar rats. S100B immunoreactivity in the DG, CA1, and CA3 and the number of S100B‐positive cells in the DG and CA3 were significantly increased in Gunn rats compared to Wistar rats. Conclusion: Our findings suggest that both microglia and astrocyte are activated in Gunn rats and their learned helplessness could be related to glial activation. [ABSTRACT FROM AUTHOR]