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Introduction: Studies have proposed that royal jelly(RJ) has various biological activities in different cells and tissues. Since it has been demonstrated that RJ contains compounds having desirable effects on central neurons system and neural functions, the present study aimed to investigate the effect of royal jelly on learning and memory in rats. Methods: Male wistar rats were divided into two groups, the royal jelly and the control. In the RJ group, the rats received a food that contained 3% RJ instead of regular food for 10 days. Then learning and memory were investigated in these animals through both passive avoidance learning test(1 day and 1 week after receiving electrical shock) and Morris water maze test(1 day and 1 week after a 4-day learning period). Results: The study results indicated that the food containing RJ in the RJ group significantly increased the time of the first entrance to the dark room one week after the electrical shock in passive avoidance learning test. In other words, the findings suggest an improvement of learning and memory in RJ group. In the acquisition phase of Morris water maze test, rats receiving RJ found the underwater escape plate during less time and distance comparing with the control group. Furthermore, one week after the acquisition phase, in the retention phase, rats spent more time in the quadrant in which the escape plate was previously located. Conclusion: The present study findings propose that Royal Jelly can improve cognitive processes through positive effects on neural functions and probably has a significant influence on prevention and therapy of some neuronal disorders.

Introduction: The nucleus accumbens is involved in various functions ranging from motivation and reward to feeding and drug addiction. Some researchers have also suggested that this region has some roles in consciousness. In the present study, the effect of electrical stimulation and lesion of nucleus accumbens on Electroencephalogram waves (EEG) of addict and non-addict rats was investigated. Method: Male wistar rats (weight 190-250 g) were divided into control and addict groups. Addiction was induced by injection of morphine (three times a day and for four days). Then all rats in both groups were aneasthetized by urethane and stainless steel electrodes were implanted in nucleus accumbens. EEG waves were recorded in three stages of control, after stimulation (130µA, 100HZ, every 5sec for 10 min), and after lesion (0.4 mA, 60 sec) of nucleus accumbens in each group. Results: In addict group alpha and betha waves were increased, while theta and dltha waves were decreased compared to intact group. Electrical stimulation and lesion of nucleus accumbens decreased theta waves in intact group and increased betha waves in addict group comparing to the control stagesConclusion: Although morphine dependency causes increase of high frequency- low voltage waves and decrease of low frequency-high voltage waves, it seems, that nucleus accumbens has no role in variations of brain waves.

ABSTRACT: Introduction & Objective: Opioid dependence has been causing limitation in usage of morphine and other opioid drugs in pain control. The aim of this study was to assess the effect of short-term forced exercise on withdrawal syndrome in morphine addicted male rats. Materials & Methods: This experimental study was done in the physiology research center of Ahwas Jondishapour University of Medical Sciences. Twenty four young male Wistar rats, weighing 200-300gr, were randomly divided into four groups: no addiction and no exercise, no addiction and exercise, addiction and no exercise and addiction and exercise. The exercise groups underwent treadmill forced exercise for ten days. The first five days morphine was administrated (ip) twice daily with increasing dose (5، 10، 20، 40, 50 mg/kg) to addicted groups. Also single dose (50mg/kg) of morphine was administrated to them on the 10th day of exercise. After administration of naloxone hydrochloride the withdrawal symptoms were evaluated for 5 minutes. The findings of this study were analyzed by SPSS software and One- way ANOVA (Tukey) test. Results: The findings of this study showed that the withdrawal symptoms was elevated in exercise and addicted groups in comparison with control group (p

Introduction:Exercise and physical activity are important factors for human health.It has been reported that exercise can be considerably useful in the teratment of psychological diseases.in the present study the effect of running on Spontaneous Electroencephalographic Activity (EEG) of rats was investigated. Method:Male wistar rats weighting 190-250 gr were selected and divided into control and exercise groups.the animals of exercise group were run on treadmill(I hour a day) for duration of two weeks.Then the animals in both groups were anesthized with urethane and EEGs of them were recorded. Result:In the exercise group alpha,beta and theta waves significantly increased and delta waves deceased in comparison to the control group. Discussion:In the present study high frequency-low voltage waves increased and low frequency-high voltage waves decreased in the exercise group.This provides further support to the earlier supposition that increase in high frequency-low oltage waves represent promotion of consciousness.It seems that exercise could increase alertness.

ABSTRACT The purpose of the present study was to investigate the effect of crocin on brain oxidative damage and memory deficits in a 6-hydroxydopamine (6-OHDA) model of Parkinson’s disease. Male Wistar rats were subjected to unilateral injection of 6-OHDA (16 µg) into the medial forebrain bundle and treated with crocin (30 and 60 mg/kg) for six weeks. The rats were tested for memory performance at six weeks after 6-OHDA infusion, and then were killed for the estimation of biochemical parameters. The increase in thiobarbituric acid reactive substances (TBARS) and nitrite levels in the hippocampus were observed in the 6-OHDA lesioned rats, which was accompanied by memory deficits in a passive avoidance test at the end of week 6. Moreover, treatment with crocin decreased TBARS and nitrite levels in the hippocampus, and improved aversive memory. The present study conclusively demonstrated that crocin acts as an antioxidant and anti-inflammatory agent in the hippocampus of parkinsonian rats and could improve aversive memory through its properties.

In recent years, there has been considerable focus on exploring driven-dissipative quantum systems, as they exhibit distinctive dissipation-stabilized phases. Among them dissipative time crystal is a unique phase emerging as a shift from disorder or stationary states to periodic behaviors. However, understanding the resilience of these non-equilibrium phases against quantum fluctuations remains unclear. This study addresses this query within a canonical parametric quantum optical system, specifically, a multi-mode cavity with self- and cross-Kerr non-linearity. Using mean-field (MF) theory we obtain the phase diagram and delimit the parameter ranges that stabilize a non-stationary limit-cycle phase. Leveraging the Keldysh formalism, we study the unique spectral features of each phase. Further, we extend our analyses beyond the MF theory by explicitly accounting for higher-order correlations through cumulant expansions. Our findings unveil insights into the modifications of the open quantum systems phases, underscoring the significance of quantum correlations in non-equilibrium steady states. Importantly, our results conclusively demonstrate the resilience of the non-stationary phase against quantum fluctuations, rendering it a dissipation-induced genuine quantum synchronous phase.

Due to genetic erosion over evolution events, the genetic diversity of domesticated safflower species for drought tolerance is limited. Wild species has been considered as useful genetic resources for improvement of abiotic stress tolerance. In this study, a cultivated species (C. tinctorius) was crossed by two wild species (C. palaestinus and C. oxyacanthus) and the genotypes were purified until advanced generations. Then, 159 safflower recombinant lines derived from three inter-specific hybridizations were investigated during two years in terms of agronomical traits and drought tolerance at the research farm of Isfahan University of Technology. The results showed that there was considerable genetic variation in most of the agronomic and seed yield related traits among parental species and also between and within three crosses. The C. palaestinus and C. tinctorius had the highest value for seed yield under both normal and drought conditions. Under normal condition, the population derived from hybridization of cultivated species with C. palaestinus showed the highest seed yield and other agronomic traits. Therefore this population was superior relative to other populations. Under stress conditions, all three populations showed a potential for drought tolerance due to the inheritance of the resistance from two wild parents. In each of the three populations, transgressive segregants were identified for drought stress tolerance. Finally, the results revealed that the progenies of these crosses could be used to improve the seed and oil yield to promote this plant in arid regions.

This experiment was conducted to study the effects of three identified isolates of Arbuscular mycorrhizal fungi (AMF) on growth, acid phosphatase enzyme activity and phenolic compounds (phenol, flavonoid and anthocyanin) of zinnia plants (Zinnia elegans L.var. Magellan Red) under water stress conditions. A factorial (two factors) experiment was planned based on a completely randomized design (CRD) with six replications at the greenhouse of Vali-e Asr University of Rafsanan, Rafsanjan, Iran. The factors included five AMF inoculation (no mycorrhizae as control, Rhizophagus irregularis, Rhizophagus intraradisces, Funneliformis mosseae, mixture of three species) and four irrigation levels (100% FC as control, 80% FC, 60% FC and 40% FC). Seedlings with four true leaves were transplanted into 1.2 L pots and immediately inoculated with each of the above symbionts. The plans were irrigated with distilled water for 50 days to obtain certain amount of infection, then four irrigation regimes were achieved for four weeks. Vegetative growth traits (leaf number, peduncle diameter, petal length, shoot and root dry weight) were reduced significantly with increasing drought stress level. Drought stress reduced chlorophyll index (SPAD) and phenolic compounds concentration. Inoculation with AMF prominently improved growth, acid phosphatase enzyme activity, chlorophyll index and phenolic compounds under drought stress, so that under 40% FC, R. irregularis, R. intraradisces, F. mosseae, and a mixture of them increased acid phosphatase enzyme activity by 58, 52, 61, 53 percent, respectively, compared to the control. In conclusion, it is suggested that AMF inoculation improves drought tolerance of zinnia plants at least in part through the enhanced uptake of slowly diffusing mineral ions such as phosphorus.

This experiment aimed to determine effects of three arbuscular mycorrhizal fungi (AMF), i.e., Rhizophagus irregularis, Rhizophagus intraradices, and Funneliformis mosseae, either singly or their mix inoculation on dry mass, photosynthesis, chlorophyll (Chl) fluorescence, leaf pigment contents, and water-use efficiency (WUE) in Zinnia elegans (var. Magellan Red) plants under different water regimes (WR). The greenhouse experiment was performed under a complete randomized design at four different WR [100% of field capacity (FC) as control, 80, 60, and 40% FC]. Our results suggested that arbuscular mycorrhizal symbiosis protected zinnia plants against WR through improving gas-exchange capacity, higher Chl and carotenoid concentrations, Chl fluorescence, and WUE. Regardless of WR, comparison of colonization percentage demonstrated that the highest colonization was recorded for mixed AMF, while mixed inoculation was not so effective for the growth promotion as the corresponding single inoculation.

In regard to the role of Aluminium in the emergence of psychological disorded in patients with chronic kidney diseases,this research project studied the acute,and chronic effects of Alluminium on different stages of memory and learning abilitis,after grouping the rats Alluminium chloride with concentrations of 1mg,5mg,10mg and 20 mg was used per kg of body weight.the Alluminium was given by intraperitioeal injection during 3 phases of 30 days,60 days and 90 days and following this a shuttle box was used to evalute its effects on memory and learning abilities.the results bindicated that plasma level of Alluminium was significantly increaced,however Alluminium at 90 mg/kg had ni significant effect on the rats ability of learning.however doeses of 1,5,10 mg/kg clearly had a significant inhibitory effect on memory and learning Abilities.tyhis inhibitory effect had a direct correlation with the duration and dose of the Alluminium injection.the highest inhibitory effect on memory and learning abilitis was achieved at 15mg/kg dose at 30 and 40 days,which was 34.5 and 52.3% respectively (p

Exposure to chronic stress impairs memory. Also, escitalopram's impact on memory remains paradoxical. Therefore, this study examined how prolonged escitalopram administration affects input-output (I/O) functions, paired-pulse ratio (PPR), and long-term potentiation (LTP) in the hippocampal CA1 area in rats that underwent predictable and unpredictable chronic mild stress (PCMS and UCMS, respectively). Male rats were randomly assigned to different groups of control (Co), sham (Sh), PCMS and UCMS (PSt and USt, respectively; 2 h/day, for 21 consecutive days), escitalopram (Esc; 10 mg/kg, i.p., for 21 days), as well as PCMS and UCMS with escitalopram (PSt-Esc and USt-Esc, respectively). The fEPSP slope, amplitude, and area under the curve (AUC) were assessed in the hippocampal CA1 area using I/O functions, PP responses, and LTP. Serum corticosterone (CORT) levels were quantified in all experimental animals. The slope, amplitude, and AUC of fEPSP in the I/O functions, and all three PP phases prior and subsequent to LTP induction significantly declined in the USt and PSt groups. Escitalopram significantly enhanced these parameters in the PSt-Esc, but not in the USt-Esc group. Serum CORT levels corroborated the electrophysiological findings among experimental groups. Both PCMS and UCMS impaired neural excitability, neurotransmission, and memory within the hippocampal CA1 area. Escitalopram improved memory impairment only under PCMS, potentially attributed to reduced serum CORT levels. However, no influence on neural excitability, neurotransmission, and memory was observed under UCMS. This suggests different escitalopram doses might be required to ameliorate simultaneous mechanisms in response to various types of chronic mild stress., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Escitalopram, a pharmacological compound, and crocin, the active compound of saffron, influence brain functions and serotonin levels. This study examined the efficacy of escitalopram with and without crocin in restoring the input-output (I/O) functions and long-term potentiation (LTP) within the hippocampal cornu ammonis 1 (CA1) region of stressed rats., Materials and Methods: Rats were divided into six groups: control (Co), sham (Sh), stress-recovery (St-Rec), stress-escitalopram (St-Esc), stress-crocin (St-Cr), and stress-escitalopram-crocin (St-Esc-Cr) groups. They underwent 14 days of restraint stress (6 h/day). After being subjected to stress, they received 14 days of escitalopram (20 mg/kg) and crocin (30 mg/kg), as well as co-administration of these two compounds during the next 14 days. The field excitatory postsynaptic potential (fEPSP) slope and amplitude were measured using I/O functions and LTP induction in the CA1 region. Corticosterone (CORT) levels were also evaluated., Results: The fEPSPs slope and amplitude in the I/O functions and LTP induction significantly decreased in stressed rats without therapeutic intervention. These variables in the I/O functions declined in rats with escitalopram administration alone. All electrophysiological parameters showed an increase in rats treated with crocin alone compared to stressed subjects without any treatment. Serum CORT levels decreased only with crocin treatment for stressed rats., Conclusion: Neural excitability and memory within the CA1 region were severely disrupted among stressed rats without any treatment. Furthermore, administering crocin alone improved neural excitability and memory post-chronic stress. Treatment with escitalopram alone also impaired neural excitability within the CA1 region. The use of escitalopram with and without crocin did not enhance memory under chronic stress., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Advanced Biomedical Research.)

Background: Chronic stress can lead to anxiety and depression. Escitalopram is a selective serotonin reuptake inhibitor (SSRI), and crocin is a natural compound derived from saffron. Both of them are used to treat these disorders in clinical and traditional medicine, respectively. This study compared the antidepressant and anxiolytic effects of escitalopram, crocin, and their combination in rats., Materials and Methods: Rats were divided into nine groups: control, sham, rest-depression, depression-rest, depression-crocin, depression-escitalopram10, depression-escitalopram20, depression-escitalopram10-crocin, and depression-escitalopram20-crocin. Forced swimming and open field tests (FST and OFT, respectively) were used to evaluate depression, anxiety, and locomotor activity., Results: In the FST, the immobility time on day 28 significantly decreased in all depressed groups that received escitalopram, crocin, and their combination compared to the rest-depression group. Whereas, conversely, the time spent at the center in the OFT was significantly higher in similar comparisons. The total distance traveled by the OFT was significantly lower in all depressed groups, except for the depression-escitalopram10 and depression-escitalopram20 groups. The total distance traveled was significantly higher in the depression-escitalopram20 compared to the rest-depression group., Conclusion: Crocin, both doses of escitalopram and their combination, reduced depression. A high dose of escitalopram, with and without crocin, was partially more effective than a low dose of escitalopram in reversing depression. There was anxiety-like behavior observed after inducing depression with and without a recovery period. Whereas, crocin alone and both doses of escitalopram, with and without crocin, decreased anxiety-like behaviors in subjects with depression. This effect may be attributed to a modulation of brain neurotransmitter ratios., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Advanced Biomedical Research.)

Long-term use of opioid drugs such as morphine can induce addiction in the central nervous system through dysregulation of the reward system of the brain. Deep brain stimulation (DBS) is a non-pharmacological technique capable of attenuating behavioral responses associated with opioid drug consumption and possesses the capability to selectively activate and target localized brain regions with a high spatial resolution. However, long-term implantation of electrodes in brain tissue may limit the effectiveness of DBS due to changes in impedance, position, and shape of the tip of the stimulation electrode and the risk of infection of nerve tissue around the implanted electrode. The main objective of the current study is to evaluate the effect of temporal interference (TI) brain stimulation on addictive behaviors of morphine-induced conditioned place preference (CPP) in rats. TI stimulation is a non-invasive technique used transcranially to modulate neural activity within targeted brain regions. It involves applying two high-frequency currents with slightly different frequencies, resulting in interference and targeted stimulation of different brain areas with the desired spatial resolution. The results indicated that TI stimulation with the amplitude of I 1 = I 2 = 0.5 mA, carrier frequency of 2 kHz, frequency difference of 25 Hz, ON-OFF stimulation frequency of 0.25 Hz, and total duration of 10 min in three consecutive days resulted in a significant reduction of morphine preference in the morphine-stimulation group in comparison with the morphine group (p < 0.001). These findings highlight the potential of TI stimulation as a modulatory intervention in mitigating the addictive properties of morphine and provide valuable insights into the therapeutic implications of this stimulation paradigm for treatment of opioid drugs in human subjects., (© 2024. The Author(s).)

Metal contamination in soil poses a significant environmental concern worldwide, necessitating effective remediation strategies such as phytoremediation. The present study investigated the effects of EDTA dosage (1.5 and 3 mmol kg -1 ) and two Trichoderma species (T. harzianum and T. aureoviride) on copper (Cu) content and growth of maize plants grown in a Cu-contaminated soil, as well as Cu fractionation in the soil. In the absence of EDTA, only inoculation with T. harzianum led to a significant increase in shoot biomass. Combining fungal inoculum with EDTA only yielded a significant increase in shoot biomass when using T. aureoviride at a low EDTA rate, highlighting the interplay between fungal species and EDTA rates on plant growth. Results also indicated that EDTA application increased Cu bioavailability, enhancing Cu dissolution and root (not shoot) Cu concentrations. Conversely, inoculation with both Trichoderma species reduced Cu mobility and bioavailability in soil, thereby decreasing the shoot Cu concentrations of plants. When combined with EDTA, only application of T. harzianum resulted in an enhanced shoot Cu concentration, whereas combined application of T. aureoviride and EDTA did not make a significant change compared to the corresponding control (no fungal inoculation, no EDTA), possibly due to a lower compatibility of the T. aureoviride isolate with EDTA. Our results demonstrated that EDTA application, in both non-inoculated and inoculated treatments, increased Cu availability by facilitating its redistribution and transformation from less plant-available fractions (residual, Fe/Mn oxide-bound, and carbonate-bound) to the more readily plant-available forms (water-soluble and exchangeable fractions). In conclusion, although individual Trichoderma application proved beneficial for phytostabilization by reducing Cu content and mitigating Cu toxicity in plants, the combined application of EDTA and a compatible Trichoderma isolate (here, the T. harzianum isolate) holds promise for enhancing the phytoextraction capacity of plants. Although using maize has the advantage of being a food crop, to optimize phytoextraction, plant species with superior metal tolerance and phytoextraction capabilities should be selected, exceeding those of maize., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: Psychological stress impairs cognitive performance and affects mood states. This study compares the effect of four types of psychological stress (crowding, relocation, isolation, and restraint) on locomotor activity, learning, and memory, as well as anxiety-like behaviors performed by the open field, elevated plus maze, and passive avoidance tests., Methods: Wistar rats were randomly assigned to different groups of crowding, relocation, isolation, and restraint stress, and control. The stress induction was administered for 21 consecutive days (6 h/day). To evaluate various types of behaviors, the open field, elevated plus maze, and passive avoidance tests were employed., Results: According to the PA test results, the latency to enter the darkroom decreased significantly in all stress groups, especially in the crowding and isolation stress groups. However, it had an inverse relationship with serum corticosterone (CORT) levels. The total dark stay time increased significantly in the restraint and crowding stress groups, and also particularly, in the isolation stress group. In the isolation stress group, the number of darkroom entries decreased significantly. All stress groups spent a significantly shorter time in the open arms of the EPM apparatus. Finally, the total distance traveled, in the open field test was significantly lower in all stress groups, particularly in the isolation stress group., Conclusion: Crowding and social isolation were the two stress types that had the most adverse effect on cognitive performance, as they induced stress-driven anxiety-like behaviors, probably due to increased CORT secretion. A high or low population of social density may create a condition, in which the nervous system could not efficiently manage stress, particularly at chronic levels., (Copyright© 2024 Iranian Neuroscience Society.)

Stress and escitalopram (an anti-stress medication) can affect brain functions and related gene expression. This study investigated the protective effects of long-term escitalopram administration on memory, as well as on hippocampal BDNF and BCL-2 gene expressions in rats exposed to predictable and unpredictable chronic mild stress (PCMS and UCMS, respectively). Male rats were randomly assigned to different groups: control (Co), sham (Sh), predictable and unpredictable stress (PSt and USt, respectively; 2 h/day for 21 consecutive days), escitalopram (Esc; 10 mg/kg for 21 days), and predictable and unpredictable stress with escitalopram (PSt-Esc and USt-Esc, respectively). The passive avoidance test was used to assess behavioral variables. The expressions of the BDNF and BCL-2 genes were assessed using real-time quantitative PCR. Latency significantly decreased in the PSt and USt groups. Additionally, latency showed significant improvement in the PSt-Esc group compared to the PSt group. The expression of the BDNF gene significantly decreased only in the USt group. BDNF gene expression significantly increased in the PSt-Esc and USt-Esc groups compared to their respective stress-related groups, whereas the expression of the BCL-2 gene did not change significantly in both PSt-Esc and USt-Esc groups. PCMS and UCMS had devastating effects on memory. Escitalopram improved memory only under PCMS conditions. PCMS and UCMS exhibited fundamental differences in hippocampal BDNF and BCL-2 gene expressions. Furthermore, escitalopram increased hippocampal BDNF gene expression in the PCMS and UCMS subjects. Hence, neurogenesis occurred more significantly than anti-apoptosis under both PCMS and UCMS conditions with escitalopram.

Date palm, typically considered a salinity-resistant plant, grows in arid and semi-arid regions worldwide, and experiences decreased growth and yields under salt stress. This study investigates the efficacy of endophytic fungi (EF) in enhancing the salinity tolerance of date palm seedlings. In this experiment, EF were isolated from date tree roots and identified morphologically. Following molecular identification, superior strains were selected to inoculate date palm seedlings (Phoenix dactylifera L., cv. Mazafati). The seedlings were subjected to varying levels of salinity stress for 4 months, utilizing a completely randomized factorial design with two factors: fungal strain type (six levels) and salinity stress (0, 100, 200, and 300 mM sodium chloride). The diversity analysis of endophytic fungi in date palm trees revealed that the majority of isolates belonged to the Ascomycota family, with Fusarium and Alternaria being the most frequently isolated genera. In this research, the application of fungal endophytes resulted in increased dry weight of roots, shoots, root length, plant height, and leaf number. Additionally, EF symbiosis with date palm seedling roots led to a reduction in sodium concentration and an increase in potassium and phosphorus concentrations in aerial parts under salt-stress conditions. While salinity elevated lipid peroxidation, consequently increasing malondialdehyde (MDA) levels, EF mitigated damage from reactive oxygen species (ROS) by enhancing antioxidant enzyme activity, including superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX), while promoting proline and total soluble sugar (TSS) accumulation. The colonization percentage generally increased with salinity stress intensity in most strains. According to the results, the application of EF can alleviate the adverse effects of salinity stress and enhance the growth of date palm seedlings under saline conditions., (© 2023. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Background: Frailty is a common problem in elderly individuals. However, this issue is not well investigated among heart failure (HF) patients with appropriate scales. We aimed to translate and evaluate Edmonton frailty scale (EFS) validity and reliability in Iranian HF adults., Methods: We implemented this methodological study on stable HF patients referred to an outpatient heart clinic in Isfahan, Iran. The translation was done using the forward-backward method. Ten individuals were asked to comment about all items in terms of understandability and simplicity. Fifteen experts were invited, and their ratings on each item were collected to measure the content validity index (CVI) and content validity ratio (CVR). Cronbach's alpha was used for the assessment of internal consistency. After completing the scale for the second time with a two-week interval, test-retest reliability with intraclass correlation coefficient (ICC) measurement was done., Results: The translation process was performed uneventfully. All items were reported to be simple and meaningful. CVI of items ranged from the minimum of 0.80 to a maximum of 1.00 plus an acceptable CVR of at least 0.60. Fifty HF patients (age: 67.2±14.1 years, males: 56%) completed the questionnaire twice without missing data. Cronbach's alpha was first to be 0.550. After omitting three items about social support, drug usage, and nutrition, the value was raised to 0.711. Test-retest reliability showed a good index of consistency (ICC: 0.693, 95% confidence interval: 0.527-0.810)., Conclusion: Modified Persian EFS is a simple and meaningful tool with high validity and acceptable reliability for assessing frailty in HF individuals irrespective of age., Competing Interests: None of the authors had any personal or financial conflicts of interest.

Background and Purpose: Previous research has found that the electrical stimulation of the ventral tegmental area (VTA) is involved in drug-dependent behaviors and plays a role in reward-seeking. However, the mechanisms remain unknown, especially the effect of electrical stimulation on this area. Therefore, this study aimed to investigate how the electrical stimulation and the temporary inactivation of VTA affect the morphine- dependent behavior in male rats., Experimental Approach: The adult Wistar male rats were anesthetized with ketamine and xylazine. The stimulation electrode (unilaterally) and the microinjection cannula (bilaterally) were implanted into the VTA, stereotaxically. Then, the rats underwent three-day of repeated conditioning with subcutaneous morphine (0.5 or 5 mg/kg) injections, in the conditioned place preference apparatus, followed by four-day forced abstinence, which altered their conditioning response to a morphine (0.5 mg/kg) priming dose on the ninth day. On that day, rats were given high- or low-intensity electrical stimulation or reversible inactivation with lidocaine (0.5 pL/site) in the VTA., Findings/results: Results showed that the electrical stimulation of the VTA with the high intensity (150 μA/rat), had a minimal effect on the expression of morphine-induced place conditioning in rats treated with a high dose (5 mg/kg) of morphine. However, the reversible inactivation of the VTA with lidocaine greatly increased place preference in rats treated with a low dose (0.5 mg/kg) of morphine. Additionally, the reinstatement of 0.5 mg/kg morphine-treated rats was observed after lidocaine infusion into the VTA., Conclusion and Implications: These results suggest that VTA electrical stimulation suppresses neuronal activation, but the priming dose causes reinstatement. The VTA may be a potential target for deep brain stimulation-based treatment of intractable disorders induced by substance abuse., Competing Interests: All authors declared no conflict of interest in this study., (Copyright: © 2023 Research in Pharmaceutical Sciences.)

The lateral habenula (LHb) has received special attention due to its role in modulating motivated behavior, stress response, and rewarding and aversive stimuli through monoamine transmission. In the present study, the involvement of the N-methyl-d-aspartate (NMDA) receptors of the LHb in the expression and acquisition phases of morphine-induced conditioned place preference (CPP) was studied in male rats. Bilateral injections of agonist/antagonist (MK-801) of NMDA receptor were performed during the conditioning sessions of the acquisition phase. In other separate groups, drugs were also injected into the LHb before the test session during the expression phase of CPP. A 5-day CPP bias paradigm was used to study the effect of injections of NMDA and MK-801 into the LHb on morphine reward-related behavior. Different doses of NMDA plus morphine reduced the CPP score during the acquisition phase, whereas MK-801 significantly increased conditioning scores during the acquisition phase of CPP. The injection of agonists and antagonists of NMDA receptors in LHb had no significant effect on CPP scores and locomotion during the expression phase of CPP, whereas the motor activity in the acquisition phase was affected by the drugs. The reduction effect of NMDA on the CPP scores during the acquisition phase was blocked by pretreatment with MK-801. Our findings also suggest that NMDA receptors in the LHb may be involved in the acquisition phase of morphine-induced CPP., (© 2023 Wiley Periodicals LLC.)

Background: Morphine and other opioids are used to manage cancer-related pain; however, the role of these drugs in cancer progression remains controversial. Emerging evidence indicates that morphine can activate Toll-like receptor 4 (TLR4) and its signaling pathways, by the way the activation and expression of TLR4 can promote melanoma. In this study, we investigated the effects of morphine on the expression of TLR4 and promotion of melanoma in mice., Methods: Mice melanoma cells (B16F10) were cultured with morphine (0.1, 1 and 10 µM) for 24 h. In the other experiment, cells were treated with morphine with or without TLR4 agonist (LPS) or antagonist (TAK-242). In in-vivo model, B16F10 cells were subcutaneously injected to C57BL/6 mice, and morphine was administrated in three different treatment protocols after developing palpable tumors (acute treatment, chronic daily injections, escalating doses of morphine). In another set of experiments, B16F10 cells were pretreated with LPS (5 µg/ml) 24 h before injection into mice. Control group received normal saline. We measured cell proliferation, the expression level of Tlr4 , Nuclear factor kappa-light-chain-enhancer of activated B cells 1 ( Nf-κb1 ) genes, TLR4 protein expression, and tumor volume., Results: Chronic, acute, and escalating doses of morphine increased tumor. Morphine increased the expression of Tlr4 and Nf-κb1 regardless of the treatment protocol used., Conclusion: Morphine increases the progression of melanoma cancer and may be related to the increased expression of TLR4. Our results suggest that morphine should be used with caution in patients with melanoma.HighlightsMorphine increases the expression of TLR4 in melanoma.Morphine increases melanoma progression.These effects are mostly observed with chronic and escalating morphine administration.

Background and Purpose: The central nucleus of the amygdala (CeA) is one of the nuclei involved in the reward system. The aim of the current study was to investigate the electrical stimulation (e-stim) effect of the CeA in combination with dopamine D1 receptor antagonist on morphine-induced conditioned place preference (CPP) in male rats., Experimental Approach: A 5-day procedure of CPP was used in this study. Morphine was administered at an effective dose of 5 mg/kg, and SCH23390 as a selective D1 receptor antagonist was administrated into the CeA. In addition, the CeA was stimulated with an intensity of the current of 150 μA. Finally, the dependence on morphine was evaluated in all experimental groups., Findings/results: Morphine significantly increased CPP. While the blockade of the D1 receptor of the CeA reduced the acquisition phase of morphine-induced CPP. Moreover, the combination of D1 receptor antagonist and e-stim suppressed morphine-induced CPP, even it induced an aversion., Conclusion and Implication: The current study suggests that the administration of dopamine D1 receptor antagonist into the CeA in combination with e-stim could play a prominent role in morphine dependence., Competing Interests: The authors declared no conflict of interest in this study., (Copyright: © 2023 Research in Pharmaceutical Sciences.)

The basolateral amygdala (BLA), which is sensitive to stress, is necessary for reward-seeking behavior and addiction. Regular exercise can produce various positive effects by affecting the BLA. Therefore, we aimed to investigate the effects of chronic stress and treadmill running (TR) on anxiety-like behavior, neuronal activity, lipid peroxidation (measured by malondialdehyde (MDA) levels, a marker for oxidative stress), and total thiol in BLA, in morphine-treated rats. Male Wistar rats were restricted in restraint stress and/or ran on the treadmill and treated with morphine (5 mg/kg) for 21 days. Anxiety-like behavior was evaluated using an elevated plus maze (EPM) and open field tests (OFTs), on day 22. On day 23, neuronal activity in BLA was assessed via single-unit recording. Finally, MDA and total thiol were assessed in BLA. Our results showed that chronic administration of morphine (5 mg/kg) did not affect anxiety-like behavior. However, the morphine-treated rats, subjected to chronic stress and exercise, showed fewer anxiety-like behaviors. Morphine increased BLA's MDA levels but it was prevented by TR. Glutamatergic and GABAergic basal neuronal activities were low in morphine-treated rats but after acute morphine application, there was a significant decrease in GABAergic neuronal activities in the morphine-exercise-stress (Mor-Exe-St) group. The results of this study showed that in morphine-treated rats, stress and exercise or their combination could have either co-directional or opposite effects to the chronic effects of morphine. These results indicate the existence of common pathways similar to endogenous opioids., (© 2022 Wiley Periodicals LLC.)

The lateral habenula (LHb), known as the brain structure of the epithalamic, plays the main role in depression and drug addiction. The glutamatergic system influences morphine reward. The effect of activation/inhibition of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors (AMPARs) in the LHb on different phases of morphine-induced conditioned place preference (CPP) remains unknown. In this research, the effect of bilateral intra-LHb microinjection of AMPARs agonist and antagonist on the acquisition and expression phases of CPP in male rats has been investigated. Different doses of NBQX, the antagonist of AMPARs, in combination with the effective dose of morphine, increased the CPP score during the acquisition phase. While AMPA, the agonist of AMPARs, significantly reduced the conditioning scores in the acquisition phase. Pretreatment with NBQX (0.5 and 1 μg/rat) reversed the inhibitory effect of AMPA (1 μg/rat) on the acquisition phase of morphine-induced CPP. The antagonist (1 μg/rat) increased the effect of a high dose of agonist (2 μg/rat) on CPP. On the other hand, NBQX significantly increased CPP scores during the expression phase. AMPA did not significantly affect CPP scores in the expression phase, but significantly reduced locomotor activity in the test phase. These results confirmed the importance of AMPARs in the LHb in morphine reward. Our data also suggest that injection of an AMPARs antagonist into the LHb may alter the AMPA-induced morphine response in a dose-dependent manner., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Background and Purpose: The lateral habenula (LHb), a key area in the regulation of the reward system, exerts a major influence on midbrain neurons. It has been shown that the gamma-aminobutyric acid (GABA)- ergic system plays the main role in morphine dependency. The role of GABA type B receptors (GABA B R s ) in the regulation of LHb neural activity in response to morphine, remains unknown. In this study, the effect of GABA B R s blockade in response to morphine was assessed on the neuronal activity in the LHb., Experimental Approach: The baseline firing rate was recorded for 15 min, then morphine (5 mg/kg; s.c) and phaclofen (0, 0.5, 1, and 2 μg/rat), a GABA B R s ' antagonist, were microinjected into the LHb. Their effects on firing LHb neurons were investigated using an extracellular single-unit recording in male rats., Findings/results: The results revealed that morphine decreased neuronal activity, and GABA B R s blockade alone did not have any effect on the neuronal activity of the LHb. A low dose of the antagonist had no significant effect on neuronal firing rate, while blockade with doses of 1 and 2 μg/rat of the antagonist could significantly prevent the inhibitory effects of morphine on the LHb neuronal activity., Conclusion and Implications: This result indicated that GABA B R s have a potential modulator effect, in response to morphine in the LHb., Competing Interests: The authors declared no conflict of interest in this study., (Copyright: © 2022 Research in Pharmaceutical Sciences.)

The lateral habenula (LHb) is a critical brain structure involved in the aversive response to drug abuse. It has been determined that the gamma-aminobutyric acid (GABA)-ergic system plays the main role in morphine dependency. The role of GABA type A receptors (GABAARs) in LHb on morphine-induced conditioned place preference (CPP) remains unknown. In this study, the effect of bilateral intra-LHb microinjection of GABAAR agonist and antagonist on the acquisition and expression phases of CPP, utilizing a 5-day CPP paradigm in male rats, was evaluated. Subcutaneous administration of different doses of morphine caused a dose-dependent CPP. Intra-LHb microinjection of the GABAAR agonist, muscimol, in combination with morphine (5 mg/kg; subcutaneously) enhanced CPP scores in the acquisition phase of morphine CPP, whereas the GABAAR antagonist, bicuculline, significantly reduced the conditioning scores in the acquisition phase. Furthermore, pretreatment with a high dose of bicuculline reversed the additive effect of muscimol during the acquisition phase, yet the low dose of antagonist had no significant effect on agonist-induced CPP scores. On the other hand, muscimol (3 µg/rat) significantly increased CPP scores in the expression phase but bicuculline did not induce a significant effect on CPP scores. Bicuculline and muscimol microinjections did not affect locomotor activity in the testing sessions. Our results confirm that GABAARs in LHb play an active role in morphine reward. In addition, microinjections of bicuculline/muscimol may alter the morphine response through the GABAergic system., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The natural aging process as well as many age-related diseases is associated with impaired metabolic adaptation and declined ability to cope with stress. As major causes of disability and morbidity during the aging process, brain disorders, including psychiatric and neurodegenerative disorders, are likely to increase across the globe in the future decades. This narrative review investigates the link among exercise and brain disorders, aging, and inflammatory biomarkers, along with the function of brain-derived neurotrophic factor. For this study, related manuscript from all databases, Google scholar, Scopus, PubMed, and ISI were assessed. Also, in the search process, the keywords of exercise, neurodegeneration, neurotrophin, mitochondrial dysfunction, and aging were used. Mitochondrial abnormality increases neuronal abnormality and brain disease during the aging process. Stress and inflammatory factors caused by lifestyle and aging also increase brain disorders. Evidences suggest that exercise, as a noninvasive treatment strategy, has antioxidant effects and can reduce neuronal lesions. Brain-derived neurotrophic factor expression following the exercise can reduce brain symptoms; however, careful consideration should be given to a number of factors affecting the results., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Exercise and addiction influence brain functions. The preventive effects of fixed and progressive forced exercises on both brain functions and body weight were investigated in morphine-addicted rats. Thirty-five rats were allocated to control, morphine, fixed exercise-morphine, and progressive exercise-morphine groups. Forced exercise was applied 1h/day for 21 days with morphine sulfate administered at doses of 10, 20, 30, 40, and 50 mg/kg for 5 consecutive days. The 50 mg/kg dose was repeated over the five subsequent days. Brain performance was evaluated using the passive avoidance test and EEG recordings. The passive avoidance test revealed no significant changes in brain functions (namely, latency, total dark stay time, and number of times entering the dark compartment). Compared to the control, the morphine group exhibited significantly lower alpha and beta waves but significantly higher delta and theta ones. Compared to the morphine group, the progressive and fixed exercise-morphine groups exhibited significant changes in their passive avoidance performance and only in the alpha wave of their EEG recordings. Progressive exercise improved learning, memory, and memory consolidation but reduced locomotor activity whereas fixed exercise affected EEG recordings in the addicted subjects. Clearly, different (fixed or progressive) exercise models produced different changes in brain functions.

Objectives: The central nucleus of the amygdala (CeA) is one of the most important areas for the morphine reward system. This study investigated the effect of electrical stimulation of CeA on morphine conditioned place preference (CPP) in male rats., Materials and Methods: After anesthetizing male Wistar rats, both electrode and cannula were implanted into CeA for stimulating (low intensity: 25 μA, and high intensity: 150 μA) and injecting (lidocaine and dopamine D2 receptor antagonist), respectively. Then, CPP induced by effective (5 mg/kg) and ineffective (0.5 mg/kg) doses of morphine was evaluated for five consecutive days (n = 6 / group)., Results: The low electrical stimulation intensity of 25 μA suppressed both acquisition and expression phases, but the high intensity of 150 µA attenuated only the expression phase. On the other hand, intra-CeA administration of dopamine D2 receptor antagonist, eticlopride (2 µg/rat), with the effective dose of morphine, decreased CPP. In addition, infusion of lidocaine into the CeA inhibited morphine-induced CPP in both acquisition and expression phases with the effective dose of morphine., Conclusion: Electrical stimulation of the CeA may play an important role in attenuating morphine induced CPP via possible changes in neurotransmitters involved in the reward system such as dopamine (DA) and gamma-aminobutyric acid (GABA)., Competing Interests: The authors declare that they do not have any conflicts of interest.

Background: Carvacrol is a natural phenolic monoterpene with anti-inflammatory and antioxidant bioactivities. Neuroinflammatory and oxidative stress responses play a crucial role in the pathogenesis of Alzheimer's disease. The present study examined the effect of carvacrol on brain tumor necrosis factor-alpha (TNF-α) level and oxidative stress as well as spatial learning and memory performances in lipopolysaccharide (LPS)-exposed rats., Materials and Methods: The rats were treated with either carvacrol (25 and 50 mg/kg) or Tween 80 for 2 weeks. Thereafter, LPS (1 mg/kg) or saline was intraperitoneally administered on days 15-19, 2 h before Morris water maze task, and treatments with carvacrol or Tween 80 were performed 30 min prior to behavioral testing. The level of TNF-α, lipid peroxidation, and total thiol concentration were measured in the hippocampus and cerebral cortex at the end of the experiment., Results: It was found that LPS-exposed rats exhibited spatial learning and memory dysfunction, which was accompanied by increased TNF-α level and lipid peroxidation, and decreased total thiol concentration in the hippocampus and/or cortex. Moreover, treatment with carvacrol at a dose of 25 mg/kg attenuated learning and memory impairments, decreased TNF-α and lipid peroxidation level in the hippocampus and cortex, and increased total thiol concentration in the cortex., Conclusion: Carvacrol exerts neuroprotective effects against LPS-induced spatial memory deficits through attenuating hippocampal TNF-α level and oxidative stress in rats., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Advanced Biomedical Research.)

In the present study, to evaluate the role of the basolateral amygdala (BLA) in morphine addiction, the BLA was stimulated electrically, or inactivated temporarily using lidocaine. The electrical stimulation (ES) was delivered to BLA with low or high intensities (LI or HI: 25 or 150 µA, respectively), and five minutes before morphine administration with effective or ineffective doses, lidocaine was microinjected into the BLA. Using a 5-day conditioned place preference (CPP) paradigm, the dependence on morphine was evaluated. The results showed that LI-ES of BLA induced CPP in both the acquisition and expression phases, in the control and the ineffective dose of morphine groups. HI-ES had no effect on CPP acquisition but induced aversion in the expression, with both effective and ineffective doses of morphine. Inactivation of BLA using lidocaine, inhibited morphine-induced CPP in both acquisition and expression phases. The results of the present study indicate the prominent role of BLA in morphine addiction and dependence. Considering the contradictory results of different intensities of ES, it can be inferred that there are different neural circuits in this area of the brain, in relation to the reward responses., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: The lack of social communication is associated with the primary risk of proper brain functions. It is reported that crocin helps relieve this problem. The present study examined the protective effect of two doses of crocin on Long-term potentiation (LTP) of hippocampal cornu ammonis 1 (CA1) area as a cellular mechanism in rats exposed to chronic social isolated stress., Methods: Rats were assigned to the control, sham, isolation stress, and two stress groups (receiving 30 and 60 mg/kg crocin). Chronic isolation stress (CIS) was induced 6 h/d, and crocin was administrated for 21 days. The field excitatory postsynaptic potential (fEPSP) slope and amplitude were measured by input/output functions and LTP induction in the CA1 area of the hippocampus. Also, the corticosterone and glucose levels were assayed in the hippocampus and frontal cortex., Results: The slope and amplitude of fEPSP severity were impaired in both input/output and LTP responses in the CIS group. Crocin at a dose of 30 and particularly 60 mg/kg improved input/output and LTP responses in the CIS group. Also, the corticosterone levels significantly increased in the frontal cortex and especially the hippocampus. In contrast, only a high dose of crocin decreased hippocampal corticosterone levels in the CIS condition. Finally, the glucose levels did not change in the hippocampus and frontal cortex in all experimental groups., Conclusion: The chronic isolation stress impaired neural excitability and Long-term plasticity in the CA1 area due to elevated corticosterone in the hippocampus and probably the frontal cortex. The low and high doses of crocin improved excitability and Long-term plasticity in the chronic isolation stress group by only decreasing corticosterone levels in the hippocampus, but not the frontal cortex., Highlights: Neuronal excitability and long-term plasticity of CA1 were impaired by chronic isolation stress.The memory was protected by low and particularly high doses of crocin in the chronic isolation stress condition.Crocin decreased the corticosterone levels in hippocampus, but not frontal cortex., Plain Language Summary: The lack of social communication (isolation stress) is associated with the primary risk of brain functions. On the other hand, crocin as one of effective components of saffron is helpful for improvement of memory. Therefore, the protective effect of two doses of crocin on cellular mechanism of memory in rats exposed to chronic social isolated stress was investigated in present study. Chronic isolation stress (CIS) was induced 6h/day, and crocin was administrated for a period of 21 days at two doses of 30 and 60 mg/kg. The electrophysiological and cellular mechanism of memory in the CA1 area of the hippocampus were investigated. Also, the corticosterone and glucose levels were assayed in the hippocampus and frontal cortex. It was concluded that the chronic isolation stress impaired neural excitability and long-term plasticity in the CA1 area due to elevated corticosterone in the hippocampus and probably the frontal cortex. The low and high doses of crocin improved excitability and long-term plasticity in the chronic isolation stress group by only decreasing corticosterone levels in the hippocampus, but not the frontal cortex. Also, the corticosterone levels significantly increased in the frontal cortex and especially the hippocampus. Also, the glucose levels did not change in the hippocampus and frontal cortex in all experimental groups., Competing Interests: Conflict of interest The authors declared no conflict of interest., (Copyright© 2022 Iranian Neuroscience Society.)

Neuroinflammation has been implicated in cognitive dysfunction and the occurrence of depression in neurodegenerative diseases. Brain-derived neurotrophic factor (BDNF) is believed to be involved with the benefits of exercise training in boosting memory and learning processes and antidepressant therapies. This study aimed to investigate the effect of forced treadmill exercise on hippocampal BDNF expression levels, depression symptoms, tactile memory and working memory in lipopolysaccharide (LPS)-treated rats. For this purpose, 40 male Wistar rats received 0.25 mg/kg of LPS or saline intraperitoneally for 9 consecutive days before exercise. They again received a single injection of 0.5 mg/kg of LPS or saline on days 20 and 41 after exercise. Exercise groups had to run on a motorized treadmill 5 days a week for 8 weeks. Following the last exercise training session, forced swim test (FST), Y maze and novel object recognition (NOR) task were performed. Finally, the hippocampus of rats was removed and used for determination of BDNF expression levels by real-time polymerase chain reaction (real-time PCR). The data showed that LPS decreased BDNF expression levels, Y maze score, and recognition index in NOR and increased immobility time in FST (p < 0.05). In contrast, forced treadmill exercise increased BDNF expression levels and improved the percentage of spontaneous alternation, recognition index, and immobility time in LPS-treated rats (p < 0.05). There was a significant correlation between BDNF expression levels with immobility time and recognition index (p < 0.05) but not with the percentage of spontaneous alternation (p > 0.05). The findings suggest that forced treadmill exercise may protect the brain of LPS-treated rats by improving the symptoms of depression and cognitive function through its effect on BDNF expression levels., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: In the present study, the effects of intra-basolateral amygdala (BLA) blockade of dopamine D1 receptor on morphine-induced conditioned place preference (CPP) were investigated in male Wistar rats., Materials and Methods: A 5-day CPP paradigm was used. Morphine was injected subsequently at effective (5 mg/kg) and ineffective (0.5 mg/kg) doses. SCH 23390 (0.5- μg/rat), as a selective D1 receptor antagonist, was microinjected bilaterally into the BLA., Results: Effective dose of morphine induced a significant CPP, and increased the locomotor activity during the testing phase. The results showed that morphine-induced CPP was significantly suppressed by D1 receptors antagonist in BLA in the acquisition phase and caused an aversion even at high doses. The antagonist also significantly prevented CPP expression. Morphine increased the motor activity, but the D1 receptors blockade, significantly reduced it., Conclusions: The findings of this study suggest a possible role for BLA dopamine D1 receptors in reward responses in morphine dependency., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Advanced Biomedical Research.)

For processing the development of psychological dependency, opioid reinforcement, and opiate-related associative reward, learning, and memory in the brain, the ventral tegmental area (VTA) is considered the key zone. As the responsible region for the morphine role in conditioned place preference (CPP), this area has an important role. So, the present research was conducted to investigate the effects of different intensities of electrical stimulation on VTA utilizing CPP, with two morphine doses. Reversible inactivation of VTA was performed via bilateral microinjection of Lidocaine into this area with two implanted separate cannulas. Our findings indicated that 5 mg/kg morphine-induced CPP was suppressed by 150 μA VTA electrical stimulation. The results also showed that bilateral Intra-VTA administration of Lidocaine significantly decreased the 5 mg/kg morphine-induced CPP acquisition phase in comparison with their respective sham group, which reversed in the reinstatement test. It should be concluded that these findings are important for the detection of mesolimbic nervous system ties and could help to find new ways to attenuate the rewarding action of morphine., (Copyright © 2021. Published by Elsevier Inc.)

Different exercise patterns, neurotransmitters, and some genes have numerous effects on learning and memory. This research aims to investigate the long-term effects of submaximal aerobic exercise on spatial memory (SM), passive avoidance learning (PAL), levels of serum relaxin-3, gamma-aminobutyric acid (GABA), RLN3 gene, and glutamic acid decarboxylase (GAD65/67 genes) in the brainstem of adult male Wistar rats. Fifty male Wistar rats were randomly divided into five groups: aerobic exercise groups, performed on a treadmill running (TR), for 5 weeks (Ex 5, n = 10), 10 weeks (Ex 10, n = 10), involuntary running wheel group for 5 weeks (IRW 5 , n = 10), sham (Sh, n = 10) and control (Co, n = 10). Consequently, SM, PAL, serum relaxin-3, GABA, and GAD65/67 and RLN3 genes were measured by ELISA and PCR. Ex 5, Ex 10 and IRW 5 improved significantly SM (p ≤ 0.05), PAL (p ≤ 0.001) and decreased significantly relaxin-3 (p ≤ 0.001). RLN3 in the brain also decreased. However, it was not significant. GABA and GAD65/GAD67 increased significantly (p ≤ 0.05) in Ex 5 , Ex 10 compared to Sh and Co. Aerobic exercise enhanced SM and PAL in Ex compared to Co and Sh. However, duration and type of exercise affected the level of enhancement. The serum relaxin-3 and RLN3 gene displayed reverse functions compared to GABA and GAD65/67 genes in Ex. Therefore, the changes of neurotransmitters in serum relaxin-3, GABA, and their genes: RLN3 and GAD65/67 respectively, influenced learning and memory meaningfully., Competing Interests: Declaration of competing interest No conflicts of interest, financial or otherwise, are declared by the authors., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The lateral habenula (LHb) plays a principal role in response to aversive stimuli and negative emotional states. In this study, we have evaluated the effects of unilateral electrical stimulation (e-stim) of the LHb on morphine-conditioned place preference (CPP), before or after bilateral injections of Gamma-aminobutyric acid-B receptor (GABA B R) antagonist, phaclofen, in male rats. Morphine (5 mg/kg; s.c.) induced a significant CPP, using a 5-day CPP paradigm. Intra-LHb microinjection of phaclofen or the LHb e-stim decreased only the acquisition of CPP. The 150 μA stimulation plus phaclofen significantly suppressed the expression phase but induced aversion in the acquisition of CPP, and an e-stim of 25 μA in combination with the antagonist, significantly prevented only the acquisition phase. The findings of this study confirm the possible role of GABA B Rs in the LHb on the acquisition and the expression of CPP. These results show that e-stim of LHb alone or plus phaclofen may change the GABA transmission, involving into CPP. Therefore, the GABAergic system, especially through GABA B Rs, may play a prominent role in the behavioral responses to morphine-induced CPP by LHb stimulation., (Copyright © 2021. Published by Elsevier B.V.)

Background: Depression affects various brain functions. According to previous studies, escitalopram influences brain functions in depression and crocin reduces memory impairments. Therefore, this study aimed to compare the therapeutic effects of using crocin and escitalopram (separately and in combination) on learning and memory in rats with stress-induced depression., Methods: Fifty-six rats were allocated into seven groups of control, sham, continuous depression, recovery period, daily injections of escitalopram, crocin and escitalopram-crocin during 14 days after inducing depression by stress. Passive avoidance (PA) test was used to assess brain functions., Results: Latency has significant differences in depression group. Also, it significantly increased in depression-crocin, depression-escitalopram and depression-escitalopram-crocin groups compared to the depression group. The dark stay (DS) time was significantly higher in the depression and depression-recovery groups. However, the DS time significantly decreased in the depression-crocin, depression-escitalopram and depression-escitalopram-crocin groups. Furthermore, the number of entrances to the dark room was significantly lower in depression-crocin and depression-escitalopram-crocin groups compared to the depression one., Conclusion: Different depression treatments (i.e. crocin, escitalopram and crocin-escitalopram) reduced depression-induced memory deficits. Crocin and escitalopram-crocin, respectively, improved brain functions and locomotor activity more than escitalopram. Comparatively, in subjects with depression, crocin, which is an effective saffron constituent, partially affected the memory deficits better than escitalopram (as a chemical component)., Competing Interests: Conflict of Interest None., (© Penerbit Universiti Sains Malaysia, 2021.)

Background: Congenital hypothyroidism (CH) is one of the most prevalent preventable causes of mental retardation. Studies show that the incidence rate of CH is very high in Iran. Disease mapping is a tool for visually expressing the frequency, incidence, or relative risk of illness. The present study aimed to model CH counts considering the effects of the neighborhood in towns and perform mapping based on the relative risk., Methods: In this historical cohort study, data of all neonates diagnosed with CH with TSH level ≥5 mIU/L between March 21, 2017, and March 20, 2018, in health centers in Guilan, Iran were used. The number of neonates with CH was zero in most towns of Guilan Province. The Bayesian spatial zero-inflated Poisson (ZIP) regression model was employed to investigate the effect of the town's neighborhood on the relative risk of CH incidence. Then, the map of the posterior mean of the relative risk for CH incidence was provided. The analysis was performed using OpenBUGS and Arc GIS software programs., Results: The relative risk of CH incidence was high in the West of Guilan. Moreover, the goodness-of-fit criterion indicated that it is more appropriate to fit the Bayesian spatial ZIP model to these data than the common model., Conclusions: Considering the high relative risk of CH in the Western towns of Guilan Province, it is better to check important risk factors in this region., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 International Journal of Preventive Medicine.)

Objectives: We investigated effect of the ventromedial hypothalamus (VMH) dopamine D2 receptor inhibition on food intake and plasma ghrelin following chronic free or scheduled meal with different caloric intakes., Methods: Male Wistar rats (220-250 g) were fed diets containing free (control) or three scheduled diets of standard, restricted and high-fat for 1 month. The animals stereotaxically received an intra VMH single dose of sulpiride (0.005 µg)/or saline (0.5 µL) before meal time. Thirty minutes later, food intake and circulating ghrelin were measured., Results: Sulpiride significantly reduced food intake and ghrelin concentration in freely fed and scheduled-standard diet (p<0.05), while increased food intake, with ghrelin level on fasted level in scheduled-restricted group (p<0.01) compared to control. Food intake and ghrelin concentration between scheduled-high fat and freely fed or scheduled-standard diets did not show significant changes., Conclusions: The VMH D2 receptors are possibly involved in controlling scheduled eating behavior, depending on energy balance context., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)