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Depression often known as depressive disorder is described by a persistent lack of enjoyment, enthusiasm in pursuits, or melancholy feelings. Depression is not the same as normal mood swings and feelings about day-to-day living. It could affect every aspect of life, including relationships with friends, family, and the community. It could be brought on by or exacerbated by problems at work or in the classroom. This study aims to evaluate antidepressant like activity of ethanolic extract of roots of Boerhavia diffusa (Nyctaginaceae). control and cure of this diseases, a vast variety of medications are used daily. The herbal drugs are biodegradable and are natural medications hence are becoming more and more popular. Using a Soxhlet equipment and a normal extraction procedure, the ethanolic extract was produced. The mice were administered several dosages of the extract (100, 200, and 400 mg/kg) in addition to the vehicle (normal saline) for the control group & ARS (Acute Restraint Stress) Group and fluoxetine as the conventional medication. The mice were subjected to ARS and were treated with ethanolic extract of Boerhavia diffusa at a dose of 100mg/kg, 200mg/kg and 400mg/kg respectively. After that they were subjected to animal models, the tail suspension test (TST), force suspension test (FST) to assess the antidepressant potential and open field test (OFT), to assess locomotor & antidepressant potential of administered drug The TST revealed prolonged immobility in the BDEE (Boerhavia diffusa ethanolic extract) treated animals. The crossing over of squares activity in the OFT rose, indicating a decline in depression levels. The mice's FST revealed a decrease in their ability to reach the plateau stage following immobility. According to the study, BDEE demonstrates strong antidepressant effect and offer a natural alternative to pharmaceutical treatment for depression disorders. In futuristic study, further investigation is required to identify certain active molecules and have a deeper comprehension of the underlying processes of action. [ABSTRACT FROM AUTHOR]

Background and objectives: Previous research has demonstrated the antidepressant potential of Avena sativa; however; its mode of action is still unknown. Hence, the role of the monoaminergic system in the antidepressant-like activity of A. sativa was investigated by using the tail suspension test in the present study. Methods: The mice intraperitoneally (i.p.) received the hydroalcoholic extract of A. sativa (50, 100, and 200 mg/kg) 30 min before the tail suspension test. The participation of the monoaminergic system in the antidepressant-like activity of A. sativa (200mg/kg) was assessed by administration of several receptor antagonists, 60 min before the administration of the extract in the test. Moreover, the effect of A. sativa on animals’ locomotion was examined by using open-field test. Results: All doses of the A. sativa extract caused a significant antidepressant-like effect (p0.05). In addition, pre-treatment of the animals with sulpiride, haloperidol, SCH23390, p-chlorophenylalanine, ketanserin, WAY100135, reserpine, yohimbine, and prazosin abolished the antidepressant-like activity of A. sativa. Furthermore, the joint administration of sub-effective doses of A. sativa with fluoxetine and imipramine produced a synergistic antidepressant-like effect. Conclusion: Avena sativa induced an antidepressant-like effect in tail suspension test that is dependent on the monoaminergic system; however; clinical studies are required for showing the beneficial effects of the extract in humans.

The majority of antidepressant medications reduce depression symptoms, but they also have a number of undesirable side effects. The hunt is on for medications that are both more effective and welltolerated. In light of this, the current investigation set out to assess the hydroalcoholic extract of Urtica Urens L.'s aerial parts' (HAUU) antidepressant potential in mice. The Tail Suspension Test (TST) and the Forced Swimming Test (FST) on mice were used to assess it. For 14 days, the HAUU (250 and 500 mg/kg, po) was given orally to distinct groups of 20-25-weight Swiss albino mice in order to conduct TST and FST testing. The presence of alkaloids, glycosides, phenols, flavonoids, and tannins was discovered through phytochemical examination. The HAUU demonstrated a dose-dependent decrease in the amount of time that mice were immobile. Mice's immobility duration was considerably shortened in both the FST and TST when 500 mg/kg of HAUU was administered. The extract's effectiveness was discovered to be on par with fluoxetine (20 mg mg/kg, po). It was discovered that when given orally at a dose of 2000 mg/kg, it was toxicologically safe and did not cause any mouse deaths. The results of the current investigation indicate that the HAUU is toxicologically safe and has strong antidepressant activity, as demonstrated by the TST and FST tests. [ABSTRACT FROM AUTHOR]

Depression is a major world health issue. Though conventional antidepressants are employed for its management, they are fraught with inconsistent efficacy and untoward side effects. Therefore, finding alternative medicines for depression treatment is critical. The present study evaluated the possible antidepressant-like properties of hydroethanolic leaf extract of Morinda longiflora (MLE) in animal models. Acute animal models—Forced swim (FST) and tail suspension tests (TST)—as well as a chronic model, open space swim test, were used to establish antidepressant-like activity. The open field test was performed to exclude confounding psychostimulatory effects. Attempts were also made to investigate the possible underlying mechanism(s) of the antidepressant-like action of MLE. Oral treatment with MLE (30–300 mg/kg) significantly decreased the duration of immobility in the TST and FST. Also, treatment of mice with para-chlorophenylalanine (PCPA, 300 mg/kg, i.p.) failed to reverse the reduction in immobility duration induced by MLE. Furthermore, after treating mice with reserpine (1 mg/kg), α-methyl-p-tyrosine (AMPT, 100 mg/kg, i.p.), or both drugs combined, the reduction in immobility duration caused by MLE was reversed. Again, the anti-immobility actions produced by the extract were significantly reversed by l-arginine, sildenafil, haloperidol and prazosin but not propranolol, yohimbine or cyproheptadine. Pre-treatment of mice with l-NAME and methylene blue potentiated the anti-immobility action produced by the extract. The extract markedly reduced the duration of immobility in the OSST model. However, the extract (30–300 mg/kg) had no significant effect on the total distance travelled in the open field test. In conclusion, the current findings suggest that hydroethanolic leaf extract of Morinda longiflora has significant antidepressant-like activity and may involve catecholaminergic and nitric oxide-cyclic guanosine monophosphate pathways.

Considering the main factor that causes or triggers depression in humans is stress. Several stress factors are applied to form depression-like symptoms in rodents. Depression tests are used to analyze the nature and patterns of depression. Well-founded modeling and versatile evaluation of tests are necessary to investigate a hypothesis that is related to depression. It is impossible to model or test all aspects of depression in humans by using experimental animals. As a result, the aims of the study should be determined specifically in depression models. The correct interpretation of the tests that are suitable for these aims is indispensable for the reliability of the data. To achieve this goal, the biological basis of the depression-related behaviors of animals should be well known. In this review, model and test concepts related to depression are discussed and behavioral patterns of rodents are explained with several examples.

Introduction: Depression is a prevalent psychiatric disorder affecting 3.8% of the global population. The clinically available antidepressants can cause serious adverse effects. Aegle marmelos fruit has shown a wide range of pharmacological effects. The present study was carried out to elucidate the possible antidepressant activity of Aegle marmelos (Bael) fruit in Swiss albino mice. Objective: To evaluate the possible antidepressant activity of Aegle marmelos fruit extract in Swiss albino mice. Methods: A total of 30 (n=30) male Swiss albino mice weighing 25-35 g, divided into five groups of six animals each were used for the study. Aegle marmelos fruit powder was subjected to solvent extraction in a soxhlet apparatus. The antidepressant activity of the hydroalcoholic extract of Aegle marmelos fruit was evaluated by using two models –Forced Swimming Test (FST) and Tail Suspension Test (TST). Results: One-way ANOVA was used for multiple comparisons followed by a post hoc (Bonferroni test) for comparison between groups. Aegle marmelos fruit at the dose of 100mg/kg and 200 mg/kg significantly reduced the immobility time in both the tests (TST and FST) compared to the control. The reduction in duration of immobility at the dose of 200 mg/kg was comparable to the standard drug Imipramine. Conclusion: The Hydroalcoholic extract of Aegle marmelos has significant antidepressant activity in both the animal models of depression (FST and TST).

BACKGROUND: 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 D2 receptor (D2R) agonists are increasingly used as adjunctive antidepressants. Nevertheless, how D2Rs influence disease-relevant patterns of prefrontal circuit activity remains unknown. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

In the current study, we investigated the effect of creatine monohydrate (CrM) and newly synthesized creatine lysinate (CrLys) in tail suspension (TST) and rotarod tests and their influence on the histology of the skeletal muscles. In the TST, a slight decrease in the immobility time from the 1st to the 3rd week was observed in the group treated with CrM at a dose of 1.5 g/kg/day and CrLys at a dose of 6 g/kg/day. The rotarod test revealed that CrM (1.5 g/kg/day) and CrLys (3 g/kg/day) lead to a significant improvement in motor coordination in the 3rd week. The results from histology showed an increase in the muscle fiber diameter of soleus muscle in animals treated with CrM (3 g/kg/day) and CrLys (6 g/kg/day). The results showed that supplementation with creatine derivatives appears to be a generally effective nutritional ergogenic aid for an improvement of physical performance. [ABSTRACT FROM AUTHOR]

Prescription drug abuse is an issue that is rapidly growing globally. Pregabalin, an anticonvulsant, analgesic, and anxiolytic medication, is effective in the management of multiple neurological disorders; however, there is increasing concern regarding its widespread illicit use. It has been previously reported in mice that pregabalin can induce conditioned place preference. In this current investigation, the potential of pregabalin to elicit free-choice drinking in a mouse model of drug addiction, and its effect on recognition and withdrawal behaviors after forced abstinence, were studied. Twenty-two male BALB/c mice were randomly divided into three groups (n = 7–8/group); control, pregabalin-30, and pregabalin-60. The study had three phases: habituation (days 1–5) with free water access, free-choice drinking (days 6–13) with pregabalin groups receiving one water and one pregabalin bottle, and forced abstinence (days 14–21) with free water access. On day 13, the first open field test was conducted, followed by the Novel Object Recognition Test. On day 21, the second open field test was performed, followed by the Tail Suspension Test and Forced Swimming Test. Pregabalin elicited voluntary drinking in the higher-dose group, concurrently causing a decline in recognition memory performance in the novel object recognition test. Moreover, pregabalin induced withdrawal behavior after a period of forced abstinence in the forced swimming and tail suspension tests. This is the first report to establish an animal model of free-choice pregabalin drinking that may be used for further molecular studies and targeted therapy for pregabalin addiction.

AbstractAcetylcholinesterase inhibitors (AChEIs) are drugs that enhance cholinergic neuro-transmission and are used for the treatment of Alzheimer’s disease and myasthenia gravis. Common AChEIs include rivastigmine, donepezil and galantamine (GAL), but they can cause side effects like nausea, vomiting, depression and bradycardia. A potential link exists between AChEIs and increased depression risk. Recently, we have discovered a hybrid compound (4b) combining GAL and curcumin (CCN), which shows improved anticholinesterase activity and neuroprotective effects. It could be developed as a potential multitarget agent for neurodegenerative disorders. Here, we examine the compound’s depressant side effect on mice, comparing it to GAL and CCN. Tests were conducted twice using the tail suspension test (TST) and the forced swim test over an 8-day treatment period. The results showed that 4b lacked the depressant effect of GAL and even displayed a mild antidepressant effect similar to CCN in TST. This suggests that incorporating antidepressant fragments, like CCN, into AChEIs can potentially neutralize their depressive side effects.

We used low and high molecular weight fluorescence tracers to investigate the entry of foreign solutes into the brain parenchyma and their exit from it by the glymphatic system, during experimentally induced depressive-like behavior in rats. The tail suspension test (TST), as an acute stressor, is known to induce such a type of behavior, considered to model the human major depressive disorder (MDD). Electroacupuncture (EAP) relieves both depressive-like behavior in rodents and the symptoms of MDD in humans. Here we report that 180 min after the intracisternal injection of the low molecular weight tracer Fluorescein-5-Isothiocianate Conjugated Dextran (FITC-d3), a 15-min duration TST tended to increase the control fluorescence in the brain of rats. Both EAP and sham EAP decreased the fluorescence of FITC-d3 in comparison with the TST, but not the control value. In addition, EAP and sham EAP counteracted the effects of TST. The high molecular weight tracer Ovalbumin Alexa Fluor 555 Conjugate (OA-45) failed to enter the brain parenchyma and accumulated at more superficial sites; however, EAP or sham EAP modified the distribution of fluorescence under TST application in a similar manner as that observed during the use of FITC-d3. It is concluded that EAP is possibly a valid treatment to slow down the entry of foreign solutes into the brain; in view of the comparable effects of EAP on FITC-d3 and OA-45 distribution, EAP seems to act before FITC-d3 passes the astroglial aquaporin-4 water channels, which are a critical constituent of the glymphatic system.

Guanosine has been considered a promising candidate for antidepressant responses, but if this nucleoside could modulate adenosine A1 (A1R) and A2A (A2AR) receptors to exert antidepressant-like actions remains to be elucidated. This study investigated the role of A1R and A2AR in the antidepressant-like response of guanosine in the mouse tail suspension test and molecular interactions between guanosine and A1R and A2AR by docking analysis. The acute (60 min) administration of guanosine (0.05 mg/kg, p.o.) significantly decreased the immobility time in the tail suspension test, without affecting the locomotor performance in the open-field test, suggesting an antidepressant-like effect. This behavioral response was paralleled with increased A1R and reduced A2AR immunocontent in the hippocampus, but not in the prefrontal cortex, of mice. Guanosine-mediated antidepressant-like effect was not altered by the pretreatment with caffeine (3 mg/kg, i.p., a non-selective adenosine A1R/A2AR antagonist), 8-cyclopentyl-1,3-dipropylxanthine (DPCPX — 2 mg/kg, i.p., a selective adenosine A1R antagonist), or 4-(2-[7-amino-2-{2-furyl}{1,2,4}triazolo-{2,3-a}{1,3,5}triazin-5-yl-amino]ethyl)-phenol (ZM241385 — 1 mg/kg, i.p., a selective adenosine A2AR antagonist). However, the antidepressant-like response of guanosine was completely abolished by adenosine (0.5 mg/kg, i.p., a non-selective adenosine A1R/A2AR agonist), N-6-cyclohexyladenosine (CHA — 0.05 mg/kg, i.p., a selective adenosine A1 receptor agonist), and N-6-[2-(3,5-dimethoxyphenyl)-2-(methylphenyl)ethyl]adenosine (DPMA — 0.1 mg/kg, i.p., a selective adenosine A2A receptor agonist). Finally, docking analysis also indicated that guanosine might interact with A1R and A2AR at the adenosine binding site. Overall, this study reinforces the antidepressant-like of guanosine and unveils a previously unexplored modulation of the modulation of A1R and A2AR in its antidepressant-like effect. [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]

Addiction to various drugs and chemicals is a significant public health concern worldwide. Addiction to prescription medications has increased due to the psychoactive effects of these medications, their availability, low price, and the lack of legal consequences for abusers. One of such prescription medication is mirtazapine (MIRT). MIRT is an antidepressant that has recently been reported to be abused and could induce withdrawal symptoms in different case studies. No previous study has investigated its abuse potential in animal models of drug addiction. Here, we conducted a free-choice drinking paradigm to investigate voluntary drinking of MIRT at two different concentrations. Male BALB/c mice were given unlimited access to two water bottles for five days before being divided into three groups: the first group had free access to two water bottles. The second group (MIRT10) and the third group (MIRT20) was allowed unlimited choice to one bottle of water and one bottle of MIRT at concentrations of 0.03 and 0.06 mg/mL, respectively. The average daily MIRT intake in the MIRT20 group was significantly higher on all tested days than that in the MIRT10 group. Moreover, mice in the MIRT20 group preferred to self-administer MIRT over water, indicating that MIRT can induce drug-seeking behavior. To further investigate the addictive potential of MIRT and its possible deterioration of memory and recognition, as reported with several known drugs of abuse, animals underwent a novel object recognition test. Mice in the MIRT20 group demonstrated significant deterioration in memory and recognition, indicating its effects on different brain regions involved in recognition, similar to other known drugs of abuse. The forced swimming test and tail suspension test were used to test MIRT-induced withdrawal symptoms after forced abstinence. After eight days of abstinence, mice in the MIRT20 group demonstrated significant depression-like symptoms in both the TST and FST, manifested by a significant increase in immobility time. MIRT was shown to induce drug-seeking behavior, deteriorate recognition, and cause withdrawal symptoms. This might confirm that MIRT has the potential to induce drug dependence and further studies are warranted to explore the neurobiological basis of MIRT-induced drug-seeking behavior.

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 studiesMaterials 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 200 mg/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.

Background and aim: Campomanesia xanthocarpa Berg. (Myrtaceae) present several pharmacological actions, but there are no reports on its antidepressant-like potential. This study investigated the antidepressant-like effect and mechanism of action of Campomanesia xanthocarpa seeds extract obtained from supercritical CO2 (40 °C, 250 bar). Experimental procedure: Mice were orally treated with the extract 1 h before the TST. To investigate the involvement of the monoaminergic system in the antidepressant-like activity of the extract, pharmacological antagonists were administered prior to the acute oral administration of the extract (60 mg/kg). Also, the interaction of the extract with antidepressants was assessed in the tail suspension test (TST). The in vitro inhibitory potential of C. xanthocarpa seeds extract towards MAO A and MAO B enzymes was tested in vitro. Results and conclusion: Animals treated with Campomanesia xanthocarpa seeds extract showed a significant reduction in the immobility time in the TST. Mice pretreatment with SCH23390, sulpiride, prazosin, yohimbine, and p-chlorophenylalanine prevented the anti-immobility effect of the extract in the TST. The combined administration of sub-effective doses of the extract with imipramine, bupropion and fluoxetine significantly reduced mice immobility time in the TST. The extract showed MAO A inhibitory activity (IC50 = 151.10 ± 5.75 μg/mL), which was greater than that toward MAO B (IC50 > 400 μg/mL).The extract of Campomanesia xanthocarpa seeds obtained by supercritical CO2 shows antidepressant-like activity, which relies on the activation of the monoaminergic neurotransmission (serotoninergic, dopaminergic and noradrenergic), suggesting that this species might represent a resource for developing new antidepressants.

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]

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]

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]

Addiction to various drugs and chemicals is a significant public health concern worldwide. Addiction to prescription medications has increased due to the psychoactive effects of these medications, their availability, low price, and the lack of legal consequences for abusers. One of such prescription medication is mirtazapine (MIRT). MIRT is an antidepressant that has recently been reported to be abused and could induce withdrawal symptoms in different case studies. No previous study has investigated its abuse potential in animal models of drug addiction. Here, we conducted a free-choice drinking paradigm to investigate voluntary drinking of MIRT at two different concentrations. Male BALB/c mice were given unlimited access to two water bottles for five days before being divided into three groups: the first group had free access to two water bottles. The second group (MIRT10) and the third group (MIRT20) was allowed unlimited choice to one bottle of water and one bottle of MIRT at concentrations of 0.03 and 0.06 mg/mL, respectively. The average daily MIRT intake in the MIRT20 group was significantly higher on all tested days than that in the MIRT10 group. Moreover, mice in the MIRT20 group preferred to self-administer MIRT over water, indicating that MIRT can induce drug-seeking behavior. To further investigate the addictive potential of MIRT and its possible deterioration of memory and recognition, as reported with several known drugs of abuse, animals underwent a novel object recognition test. Mice in the MIRT20 group demonstrated significant deterioration in memory and recognition, indicating its effects on different brain regions involved in recognition, similar to other known drugs of abuse. The forced swimming test and tail suspension test were used to test MIRT-induced withdrawal symptoms after forced abstinence. After eight days of abstinence, mice in the MIRT20 group demonstrated significant depression-like symptoms in both the TST and FST, manifested by a significant increase in immobility time. MIRT was shown to induce drug-seeking behavior, deteriorate recognition, and cause withdrawal symptoms. This might confirm that MIRT has the potential to induce drug dependence and further studies are warranted to explore the neurobiological basis of MIRT-induced drug-seeking behavior. [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]

Cannabis is an annual herbaceous plant sometimes grown for decoration and used as bird food that looks like flax. The study wanted to determine if a Cannabis extract may have an effect on how anxious and depressed the female mice behaved. forty healthy female mice were divided into four groups. Tap water was administered to the first group (control). Ethanol was administered to second group (positive control). The third and four groups were given 1 and 2 mg/kg cannabis extract respectively. Treatment continued for 14 days. After therapy, the light–dark chamber, forced swimming, tail suspension, plus lamb and open field tests were done to assess anxiety and depressive behavior. The results indicated that the anxiety and depression were increased in treated females significantly compared to control. Biochemical results showed that DA,5-HT, AChE, GSH, GST, CAT and SOD were decreased while TBARS, corticosterone and cortisol were increased. In conclusion, cannabis effects this kind of females’ behavior but the mechanisms are not clear yet. We need more researches on this trend.

Terminalia chebula (T.chebula) fruit is referred as “King of Medicines” in Tibet and is listed as a key plant in “Ayurvedic Materia Medica” due to its diverse pharmacological activity. The present study was aimed to investigate the comorbid antidepressant-like and anxiolytic-like effects of ethanol extract from T.chebula fruit using experimental behavioral tests in mice. In addition, the study explored the effects of extract on monoamine oxidase –A (MAO-A) levels in mouse brain. Two doses of the T.chebula extract (100 or 200 mg/kg, p.o.) were treated continuously for fifteen days to mice. Regarding antidepressant-like effects, the treatment of T.chebula extract at both dose (100 or 200 mg/kg, p.o.) levels resulted with significant (p

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]

It was aimed to synthesize some novel piperidine derivatives and investigate their antidepressant- like activities, in this study. Targeted compounds were obtained by reacting 1-(4-(substitutedpiperidin- 1-yl)phenyl)ethan-1-one and heterocyclic aldehydes in methanol. The structures of the synthesized compounds were determined using data from various spectroscopic methods (IR, 1H-NMR, 13C-NMR, and LCMSMS). The compounds (50 mg/kg) were tested for their antidepressant-like effects by tail suspension and modified forced swimming tests (MFST). In addition, possible alterations in the locomotor activities of mice were evaluated by activity cage measurements. Obtained results showed that compounds 2c-2f reduced the immobility time of mice in both of the antidepressant activity-screening tests indicating that these derivatives have antidepressant-like effects. Moreover, in MFST, compounds 2c and 2e significantly increased the swimming times, while compounds 2d and 2f significantly prolonged the climbing durations. Antidepressant-like effects of the compounds 2c and 2e were reversed with p-chlorophenylalanine methyl ester (serotonin depleting agent) pre-treatments while the same effect caused by the compounds 2d and 2f was abolished by pretreatment with α-methyl-para-tyrosine methyl ester (catecholamine depleting agent) pre-administrations. Moreover, pre-treatment with naloxone reversed the antidepressant-like effects of these four derivatives. Obtained results indicated that monoaminergic and opioidergic systems mediated the antidepressant-like effects of our novel piperidine derivatives. [ABSTRACT FROM AUTHOR]

The main goal of this study was to determine the antidepressant-like potential of the co-administration of sodium selenite (Se) and the selective adenosine A1 and A2A antagonists DPCPX and istradefylline (IST), respectively, in mice despair tests. Biochemical studies were performed to elucidate the action mechanisms of the investigated treatment strategies. The results confirmed that, when administered by itself, Se exerts an antidepressant-like effect in the FST and TST and that this activity is dose-dependent. Further experiments demonstrated that Se (0.25 mg/kg) significantly enhanced the activity of mice in both tests when co-administered with DPCPX (1 mg/kg) and IST (0.5 mg/kg) at doses which would be ineffective if administered individually. Our research revealed that neither DPCPX, IST, nor Se or combinations of the tested substances induced significant changes in the brain-derived neurotrophic factor (BDNF) levels in mice serum vs. the NaCl-treated group. However, we observed a decrease in the mRNA level of antioxidant defense enzymes. Molecular studies also showed changes in the expression of the Slc6a15, Comt, and Adora1 genes, particularly after exposure to the combination of Se and DPCPX, which indicates a beneficial effect and may help to explain the key mechanism of the antidepressant effect. The combination of Se with substances attenuating adenosine neurotransmission may become a new therapeutic strategy for patients with depression. [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 N-acetylcysteine 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 N-acetylcysteine). The antioxidant supplementation with NAC diminished cisplatin-induced oxidative damage and pro-apoptotic action in the prefrontal cortex, and significantly influenced specific behavioral alterations.

Biphenyl Dimethyl Dicarboxylate (DDB); is an analogue of schisandrin C, a component isolated from Fructus Schisandrae Chinensis. It is now attracting growing attention for its polypharmacotherapeutic properties as an antiviral, hepatoprotective, and immunomodulator. It’s been additionally possessed neurobehavioral impacts on experimental animals. Thus, the wide use of DDB, along with its neurobehavioral impacts; has encouraged us to study its antidepressant potential using the forced swimming test (FST). Furthermore, the protocol for FST was modified by combining it with the tail suspension test. The effect of DDB (100 mg/kg/day, p.o., 7 days) on combined technique was evaluated against fluoxetine (15 mg/kg, i.p., single dose). In the end, the brains were dissected; serotonin (5-HT), dopamine (DA), and norepinephrine (NE) levels were measured. The results demonstrated that DDB decreased immobility in FST time as fluoxetine. Furthermore, DDB elevated 5HT, NE, and DA. DDB may be useful as a supportive antidepressant drug in hepatic diseased patients. However, more clinical studies are needed to ensure its safety.

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 dorsal raphe nucleus (DRN) is a major source of serotonin in the central nervous system, which is closely related to depression-like behaviors and is modulated by local GABAergic interneurons. Although serotonin neurons are known to be activated by struggling behavior in tail suspension test (TST), the exact electrophysiological characteristics are still unclear. Here, we combined in vivo electrode recording and behavioral test to explore the mice neuron electrophysiology in DRN during TST and observed that gamma oscillation was related to despair-like behaviors whereas burst fraction was crucial for survival-like behaviors. We reported the identification of a subpopulation of DRN neurons which change their firing rates when mice get into and during TST immobile states. Both increase (putative despair units, D units for short) and decrease (putative survival units, S units for short) in firing rate were observed. Furthermore, using optogenetics to identify parvalbumin-positive (PV+) and serotonin transporter-positive (SERT+) neurons, we found that SERT+ neurons were almost S units. Interestingly, those that have been identified PV+ neurons include ~20% of D units and ~50% of S units. These results suggest that electrophysiological characteristics incorporated in despair-like behavior studies can provide new insight into the study of anti-depression targets, and GABAergic interneuron is a complex key hub to the coding and regulation of local neural network. [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]

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]

The dorsal raphe nucleus (DRN) is a major source of serotonin in the central nervous system, which is closely related to depression-like behaviors and is modulated by local GABAergic interneurons. Although serotonin neurons are known to be activated by struggling behavior in tail suspension test (TST), the exact electrophysiological characteristics are still unclear. Here, we combined in vivo electrode recording and behavioral test to explore the mice neuron electrophysiology in DRN during TST and observed that gamma oscillation was related to despair-like behaviors whereas burst fraction was crucial for survival-like behaviors. We reported the identification of a subpopulation of DRN neurons which change their firing rates when mice get into and during TST immobile states. Both increase (putative despair units, D units for short) and decrease (putative survival units, S units for short) in firing rate were observed. Furthermore, using optogenetics to identify parvalbumin-positive (PV+) and serotonin transporter-positive (SERT+) neurons, we found that SERT+ neurons were almost S units. Interestingly, those that have been identified PV+ neurons include ~20% of D units and ~50% of S units. These results suggest that electrophysiological characteristics incorporated in despair-like behavior studies can provide new insight into the study of anti-depression targets, and GABAergic interneuron is a complex key hub to the coding and regulation of local neural network.

Lobna A Saleh,1– 3 Farooq M Almutairi,2,4 Wejdan K Alorabi,1 Bashayr A Alkuhayli,1 Shaden S Alzaidi,1 Shahad B Alzahrani,1 Futun A Aljumayi,1 Maram H Abduljabbar,1 Ayidh S Alharthi,1 Mashhour A Alsufyani,1 Mohammed H Alhazmi,1 Abdulbari A Althobaiti,1 Fahad N Almutairi,1 Fahad S Alshehri,5 Ebtehal Altowairqi,1 Yusuf S Althobaiti1,2,6 1Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, Taif, 21944, Saudi Arabia; 2Addiction and Neuroscience Research Unit, College of Pharmacy, Taif University, Taif, Saudi Arabia; 3Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 4Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, University of Hafar Al-Batin, Hafar Al-Batin, Saudi Arabia; 5Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia; 6General Administration for Precursors and Laboratories, General Directorate of Narcotics Control, Ministry of Interior, Riyadh, Saudi ArabiaCorrespondence: Yusuf S AlthobaitiDepartment of Pharmacology and Toxicology, College of Pharmacy, Taif University, Health Science Campus, P.O. Box 11099, Airport Road, Al Haweiah, Taif, 21944, Saudi ArabiaTel +966 545736200Email ys.althobaiti@tu.edu.saPurpose: 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.Keywords: depression, natural supplements, tail suspension test, forced swimming test

Abstract Background Dicranopteris linearis L. is among the popular tribal plants used for various ailments, although many of its pharmacological potentials have not been investigated yet. The neuropharmacological potentials of the leaf, including sedative-anxiolytic potential, were previously studied however, the antidepressant activity was yet to be examined. Thus, this study was aimed to investigate the serotonergic, noradrenergic and opioidergic response of D. linearis leaf extracts. Methods The plant leaf was extracted in three solvents- water (DLAQ), ethanol (DLET) and ethyl acetate (DLEA) and applied each in 200 and 400 mg.kg− 1 per body weight of Swiss Albino mice. Forced Swim Test (FST) and Tail Suspension Test (TST) were conducted to evaluate antidepressant potential. In FST, latency and duration of immobility, swimming and climbing time were recorded. In TST, immobility, swinging, curling and pedaling were observed. Alongside, preliminary screening through acute toxicity study and pentobarbitone induced sleep test were performed. Results Both in FST and TST, the duration of immobility was reduced by the standard imipramine and DLET 200 and 400. In FST, DLEA 200 and 400 increased the climbing time suggesting noradrenergic mechanism of action and decreased the swimming time suggesting deficit of serotoninergic mechanism of action. Interestingly, DLET increased both the parameters presenting a dual action. However, in TST, DLEA decreased immobility but increased swinging and curling response which indicated its opioidergic mechanism. On the other hand, DLET proved to mediate through serotonin and/or NA reuptake mechanism by having decreased curling time. Conclusion Among the three extracts, the ethanol extract proved to be more potent. DLET mimicked the standard imipramine in all parameters except for the curling behavior. The result thus suggests D. linearis as a potent antidepressant agent however, recommends its medicinal use after further investigation to identify bioactive compounds.

The aim of this study was to evaluate the antistress activity of rhizomes ethanolic extract of Curculigo orchioides Gaertn in vivo, using mice with stress-induced injury. The effect of Curculigo orchioides on motor coordination, spontaneous locomotor activity, immobility time, and analgesia was evaluated in mice using standard procedure. The ethanolic extract of Curculigo orchioides at dose levels, i.e., 100 and 200 mg/kg shows pronounced antistress activity evidenced by reduced immobility time in forced swimming and tail test. It also improved motor coordination and enhanced analgesic effect compared to standard diazepam. The Curculigo orchioides was found to be a antistress activity.

Ischemic brain injury causes neuronal death and inflammation. Inflammation activates protein-tyrosine phosphatase 1B (PTP1B). Here, we tested the significance of PTP1B activation in glutamatergic projection neurons on functional recovery in two models of stroke: by photothrombosis, focal ischemic lesions were induced in the sensorimotor cortex (SM stroke) or in the peri-prefrontal cortex (peri-PFC stroke). Elevated PTP1B expression was detected at 4 days and up to 6 weeks after stroke. While ablation of PTP1B in neurons of neuronal knockout (NKO) mice had no effect on the volume or resorption of ischemic lesions, markedly different effects on functional recovery were observed. SM stroke caused severe sensory and motor deficits (adhesive removal test) in wild type and NKO mice at 4 days, but NKO mice showed drastically improved sensory and motor functional recovery at 8 days. In addition, peri-PFC stroke caused anxiety-like behaviors (elevated plus maze and open field tests), and depression-like behaviors (forced swimming and tail suspension tests) in wild type mice 9 and 28 days after stroke, respectively, with minimal effect on sensory and motor function. Peri-PFC stroke-induced affective disorders were associated with fewer active (FosB+) neurons in the PFC and nucleus accumbens but more FosB+ neurons in the basolateral amygdala, compared to sham-operated mice. In contrast, mice with neuronal ablation of PTP1B were protected from anxiety-like and depression-like behaviors and showed no change in FosB+ neurons after peri-PFC stroke. Taken together, our study identifies neuronal PTP1B as a key component that hinders sensory and motor functional recovery and also contributes to the development of anxiety-like and depression-like behaviors after stroke. Thus, PTP1B may represent a novel therapeutic target to improve stroke recovery. All procedures for animal use were approved by the Animal Care and Use Committee of the University of Ottawa Animal Care and Veterinary Service (protocol 1806) on July 27, 2018.

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.

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.

Depression affects women nearly twice as frequently as men. In contrast, rodent models of depression have shown inconsistent results regarding sex bias, often reporting more depression-like behaviors in males. This sex discrepancy in rodents modeling depression may rely on differences in the baseline activity of males and females in depression-related behavioral tests. We previously showed that the baseline despair and anhedonia behaviors, major endophenotypes of depression, are not sex biased in young adolescent wild-type mice of C57BL/6N, DBA/2, and FVB/N strains. Since the prevalence of depression in women peaks in their reproductive years, we here investigated sex differences of the baseline depression-like behaviors in adult mice using these three strains. Similar to the results in young mice, no difference was found between adult male and female mice in behavioral tests measuring despair in both tail suspension and forced swim tests, and anhedonia in the sucrose preference test. We then extended our study and tested apathy, another endophenotype of depression, using the splash test. Adult male and female mice showed significantly different results in the baseline apathy-like behaviors depending on the investigated strain. This study dissects the complex sex effects of different depression endophenotypes, stresses the importance of considering strain, and puts forward a hypothesis of the inconsistency of results between different laboratories investigating rodent models of depression. [ABSTRACT FROM AUTHOR]

Depression affects women nearly twice as frequently as men. In contrast, rodent models of depression have shown inconsistent results regarding sex bias, often reporting more depression-like behaviors in males. This sex discrepancy in rodents modeling depression may rely on differences in the baseline activity of males and females in depression-related behavioral tests. We previously showed that the baseline despair and anhedonia behaviors, major endophenotypes of depression, are not sex biased in young adolescent wild-type mice of C57BL/6N, DBA/2, and FVB/N strains. Since the prevalence of depression in women peaks in their reproductive years, we here investigated sex differences of the baseline depression-like behaviors in adult mice using these three strains. Similar to the results in young mice, no difference was found between adult male and female mice in behavioral tests measuring despair in both tail suspension and forced swim tests, and anhedonia in the sucrose preference test. We then extended our study and tested apathy, another endophenotype of depression, using the splash test. Adult male and female mice showed significantly different results in the baseline apathy-like behaviors depending on the investigated strain. This study dissects the complex sex effects of different depression endophenotypes, stresses the importance of considering strain, and puts forward a hypothesis of the inconsistency of results between different laboratories investigating rodent models of depression.

Cannabis is an annual herbaceous plant sometimes grown for decoration and used as bird food that looks like flax. The study wanted to determine if a Cannabis extract may have an effect on how anxious and depressed the female mice behaved. forty healthy female mice were divided into four groups. Tap water was administered to the first group (control). Ethanol was administered to second group (positive control). The third and four groups were given 1 and 2 mg/kg cannabis extract respectively. Treatment continued for 14 days. After therapy, the light–dark chamber, forced swimming, tail suspension, plus lamb and open field tests were done to assess anxiety and depressive behavior. The results indicated that the anxiety and depression were increased in treated females significantly compared to control. Biochemical results showed that DA,5-HT, AChE, GSH, GST, CAT and SOD were decreased while TBARS, corticosterone and cortisol were increased. In conclusion, cannabis effects this kind of females' behavior but the mechanisms are not clear yet. We need more researches on this trend. [ABSTRACT FROM AUTHOR]

Depression is a major neuropsychiatric disorder, decreasing the ability of hundreds of millions of individuals worldwide to function in social, academic, and employment settings. Beyond the alarming public health problem, depression leads to morbidity across the entire age including adolescence and adulthood. Modeling depression in rodents has been used to understand the pathophysiological mechanisms behind this disorder and create new therapeutics. Although women are two times more likely to be diagnosed with depression compared to men, behavioral experiments on rodent models of depression are mainly performed in males based on the assumption that the estrous cycles in females may affect the behavioral outcome and cause an increase in the intrinsic variability compared to males. Still, the inclusion of female rodents in the behavioral analysis is mandatory to establish the origin of sex bias in depression. Here, we investigated the baseline depression-like behaviors in male and female mice of three adolescent wild-type inbred strains, C57BL/6N, DBA/2, and FVB/N, that are typically used as background strains for mouse models of neuropsychiatric disorders. Our experiments, performed at two different developmental stages during adolescence (P22–P26 and P32–P36), revealed strain but no sex differences in a set of depression-related tests, including tail suspension, sucrose preference and forced swim tests. Additionally, the 10-day interval during this sensitive period uncovered a strong impact on the behavioral outcome of C57BL/6N and FVB/N mice, highlighting a significant effect of maturation on behavioral patterns. Since anxiety-related behavioral tests are often performed together with depression tests in mouse models of neuropsychiatric disorders, we extended our study and included hyponeophagia as an anxiety test. Consistent with a previous study revealing sex differences in other anxiety tests in adolescent mice, male and females mice behaved differently in the hyponeophagia test at P27. Our study gives insight into the behavioral experiments assessing depression and stresses the importance of considering strain, age and sex when evaluating neuropsychiatric-like traits in rodent models. [ABSTRACT FROM AUTHOR]

Objective: Acorus calamus (AC) L. (Araceae) is an annual semi-aquatic and aromatic plant found in Europe, North America and Asia. Its rhizomes are often used by Native Americans, Americans, and Chinese as well as by other cultures. Ethnobotanical studies and documents have shown their use in various disease treatments, such as insomnia, mental disorders, diabetes mellitus, epilepsy, inflammation, asthma, neuropathic pain, and diarrhea. In this study, the antidepressant activity of methanolic and hydroalcoholic extracts of the AC rhizome part in mice was investigated. Methods: Three doses of methanolic extract of AC rhizome (MEACR) (25, 50 and 100 mg/kg b.wt), three doses of hydroalcoholic extract of AC rhizome (HAACR) (100, 200 and 400 mg/kg b.wt), and standards (imipramine, 15 mg/kg b.wt and fluoxetine, 20 mg/kg b.wt) was daily oral administration to the mice for consecutive 14 days. The extract effect on the immobility time was monitored by a tail suspension test (TST) and a forced swimming test (FST). Monoamine oxidase (MAO) levels were also analyzed using standard methods. Results: The optimum antidepressant activity was viewed at 100 mg/kg b.wt of MEACR extract and 400 mg/kg b.wt of HAACR extract with 23.82% and 20.59% immobility period reduction, respectively. Besides, the extracts weakened the FST-induced elevation of MAO activity significantly and returned to near-normal levels of neurotransmitters in the brain. 100 mg/kg b.wt or above of MEACR extract significantly prevented the MAO-A and MAO-B activities in mice brain at a dose-dependent fashion. But, just 400 mg/kg b.wt of HAACR extract prevented the activity of MAO-A and MAO-B. Fluoxetine and imipramine showed a tendency to prevent the activity of MAO-A and MAO-B. Conclusion: This study suggests that AC rhizome extract mediated antidepressant activity by modulating the central neurochemical and hypothalamic-pituitary-adrenal (HPA) axis in response to FST and TST-induced stress. Therefore, AC rhizome extract can be used as a valuable plant supplement to treat depressive disorders.

Aim. Evaluation of the impact of tetrahydropyrido[2,1-b][1,3,5]thiadiazine derivatives on L-DOPA effects in the tail suspension test.Materials and methods. Some tetrahydropyrido[2,1-b][1,3,5]thiadiazines exhibit a pronounced antidepressant and adaptogenic activity. We selected compounds that demonstrated the most potent antidepressant effect in the Porsolt’s forced swim test. We chose to combine two approaches in the study: estimation of the antidepressant drug impact on levodopa effects and the tail suspension test. Caffeine sodium benzoate, amitriptyline and fluoxetine were chosen as the reference compounds. Studies of the 1,3,5-thiadiazine effects on levodopa activity were undertaken to ground detailed downstream analyses of associated responses in the dopaminergic neurotransmitter system. We measured the rectal temperature in laboratory rats prior to and after tail suspension and the total active time during 5 min in the test.Results. Administration of levodopa at a dose of 150 mg/kg led to a reduction in rectal temperature and the total time of physical activity in rats in the tail suspension test. The dosage of 500 mg/kg led to a temperature increase of 0.7°C prior to and after the stress and a longer maintenance of physical activity. Rats exhibited exophthalmos and polyuria.Levodopa at a 150 mg/kg dosage in combination with caffeine sodium benzoate did not cause a significant increase in the body temperature and prolonged physical activity by 69% in the test vs. the control group. Amitriptyline in combination with levodopa at a dose of 150 mg/kg triggered a temperature increase of 1.3°C prior to and 1.85°C after tail suspension, thus leading to a prolonged physical activity. Levodopa at a dose of 150 mg/kg in combination with fluoxetine led to elevation of the body temperature by 0.6°C prior to and 0.55°C after the stress. The total active time exhibited a declining trend.The substance TD-0348 reveals an antidepressant activity. Physical active time increased by 32% in the test vs. the control group. Temperature elevation by 1.15°C prior to and 1.25°C after the stress suggests activation of the autonomic nervous system. TD-0470 in combination with levodopa (150 mg/kg) led to a rectal temperature elevation by 0.4°C prior to and 0.7°C after tail suspension. Physical activity was prolonged compared to the levodopa-treated group (150 mg/ kg). TD-0479 led to a temperature elevation by 0.85°C prior to and 0.95°C after the stress and caused polyuria. Treatment with TD-0164 did not provide sufficient data to suggest an impact on dopamine metabolism.Conclusions. The compounds TD-0348, TD-0470 and TD-0479 affect physiological processes in experimental rats in response to treatment with L-DOPA at a dose of 150 mg/kg, which suggests the autonomic nervous system (ANS) activation. TD-0470 exhibits antidepressant properties. Treatment with TD-0164 does not provide sufficient data to evaluate its dopamine-related effects.

Abstract Background Cannabis contains Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) as the primary constituents responsible for pharmacological activity. However, there are numerous additional chemically-related structures to Δ9–THC and CBD that are pharmacologically active and may influence the pharmacological properties of Δ9-THC and CBD. This study chemically characterized the cannabinoid constituents in a series of cannabis chemovar extracts and investigated the potential cannabinoid entourage effect in two behavioral assays. Methods Six chemovar extracts were compared to pure Δ9-THC, CBD and morphine for effects on the following behavioral assays in mice: hot plate and tail suspension. The battery of behavioral tests was conducted post intravenous administration of cannabis chemovar extract. Cannabinoid profiles of extracts were analyzed using high performance liquid chromatography. Cannabis extracts were administered at equal doses of Δ9-THC to investigate the role of their cannabinoid profiles in modulating the effects of Δ9-THC. Dose response curves were fit using a log[inhibitor] vs response three parameter model and differences between group means were determined using a one-way ANOVA followed by a post hoc test. Results Cannabis chemovars tested in this study exhibited substantially different cannabinoid profiles. All chemovars produced dose-dependent immobility in the tail suspension assay and dose-dependent antinociception in the hot plate assay. The maximum antinociceptive effect and ED50 was comparable between cannabis chemovars and Δ9-THC. Two cannabis chemovars produced significantly greater immobility in the tail suspension test, with no significant differences in ED50. Conclusions Commercially available cannabis chemovars vary widely in cannabinoid content, but when equalized for Δ9-THC content, they produce similar behavioral effects with two exceptions. These findings provide only limited support for the entourage hypothesis. Further studies are necessary to characterize the nature of these pharmacological differences between cannabis chemovars and pure Δ9-THC.

Abstract 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.