Light-dark Box Test Research Articles

Synthesis, Characterization and Biocompatibility of Holmium Zirconate/Zinc Sulphide Nanocomposite in Albino Mice in a Gender Specific Manner

Aim of this study was to report the biocompatibility of Holmium zirconate, zinc sulphide and holmium zirconate/zinc sulphide (HO2Zr2O7/ZnS) nanocomposite in albino mice. Holmium zirconate, zinc sulphide and holmium zirconate/zinc sulphide (Ho2Zr2O7/ZnS) nanocomposite were synthesized by, normal microemulsion, chemical co-precipitation and two step synthesis method, respectively. The synthesized materials were characterized by X-ray diffraction (XRD) for the confirmation of phase while scanning electron microscopy (SEM) was used morphological analysis. The composition and the particle size distribution were confirmed by energy dispersive spectroscopy and particle size analysis respectively. Seven week old mice were divided into two groups in a gender specific manner: control group that were intraperitoneally injected with saline solution and treated group were administered with 50 mg/ml solvent/Kg body weight of Holmium zirconate/zinc sulphide nanocomposite for 22 days. A series of neurological tests, blood cell count, selected serum parameters and biomarkers of oxidative stress were analysed in vital organs of both treatments. It was observed that nanocomposite treated female mice remained mobile (P = 0.05) for longer time while both male (P = 0.03) and female (P = 0.02) mice had more rotations than saline treated mice during open field test. Nanocomposite treated male had reduced stretch attend reflex during light dark box test. Blood and serum parameters remained unaffected (P ˃ 0.05) when compared between nanocomposite treated and untreated mice of both genders. Malondialdehyde concentration was significantly elevated (P = 0.04) in liver of male while superoxide dismutase concentrations were significantly reduced (P = 0.05) in brain of female albino mice treated with nanocomposite than their respective control groups.

Synthesis, Characterization and Biocompatibility of Holmium Zirconate/Zinc Sulphide Nanocomposite in Albino Mice in a Gender Specific Manner

Aim of this study was to report the biocompatibility of Holmium zirconate, zinc sulphide and holmium zirconate/zinc sulphide (HO2Zr2O7/ZnS) nanocomposite in albino mice. Holmium zirconate, zinc sulphide and holmium zirconate/zinc sulphide (Ho2Zr2O7/ZnS) nanocomposite were synthesized by, normal microemulsion, chemical co-precipitation and two step synthesis method, respectively. The synthesized materials were characterized by X-ray diffraction (XRD) for the confirmation of phase while scanning electron microscopy (SEM) was used morphological analysis. The composition and the particle size distribution were confirmed by energy dispersive spectroscopy and particle size analysis respectively. Seven week old mice were divided into two groups in a gender specific manner: control group that were intraperitoneally injected with saline solution and treated group were administered with 50 mg/ml solvent/Kg body weight of Holmium zirconate/zinc sulphide nanocomposite for 22 days. A series of neurological tests, blood cell count, selected serum parameters and biomarkers of oxidative stress were analysed in vital organs of both treatments. It was observed that nanocomposite treated female mice remained mobile (P = 0.05) for longer time while both male (P = 0.03) and female (P = 0.02) mice had more rotations than saline treated mice during open field test. Nanocomposite treated male had reduced stretch attend reflex during light dark box test. Blood and serum parameters remained unaffected (P ˃ 0.05) when compared between nanocomposite treated and untreated mice of both genders. Malondialdehyde concentration was significantly elevated (P = 0.04) in liver of male while superoxide dismutase concentrations were significantly reduced (P = 0.05) in brain of female albino mice treated with nanocomposite than their respective control groups.

Synthesis, Characterization and Biocompatibility of Holmium Zirconate/Zinc Sulphide Nanocomposite in Albino Mice in a Gender Specific Manner

Aim of this study was to report the biocompatibility of Holmium zirconate, zinc sulphide and holmium zirconate/zinc sulphide (HO2Zr2O7/ZnS) nanocomposite in albino mice. Holmium zirconate, zinc sulphide and holmium zirconate/zinc sulphide (Ho2Zr2O7/ZnS) nanocomposite were synthesized by, normal microemulsion, chemical co-precipitation and two step synthesis method, respectively. The synthesized materials were characterized by X-ray diffraction (XRD) for the confirmation of phase while scanning electron microscopy (SEM) was used morphological analysis. The composition and the particle size distribution were confirmed by energy dispersive spectroscopy and particle size analysis respectively. Seven week old mice were divided into two groups in a gender specific manner: control group that were intraperitoneally injected with saline solution and treated group were administered with 50 mg/ml solvent/Kg body weight of Holmium zirconate/zinc sulphide nanocomposite for 22 days. A series of neurological tests, blood cell count, selected serum parameters and biomarkers of oxidative stress were analysed in vital organs of both treatments. It was observed that nanocomposite treated female mice remained mobile (P = 0.05) for longer time while both male (P = 0.03) and female (P = 0.02) mice had more rotations than saline treated mice during open field test. Nanocomposite treated male had reduced stretch attend reflex during light dark box test. Blood and serum parameters remained unaffected (P ˃ 0.05) when compared between nanocomposite treated and untreated mice of both genders. Malondialdehyde concentration was significantly elevated (P = 0.04) in liver of male while superoxide dismutase concentrations were significantly reduced (P = 0.05) in brain of female albino mice treated with nanocomposite than their respective control groups.

A Comparative Study on Depression and Anxiety of Mice (Mus musculus) on a Prebiotic-supplemented Diet Versus a Standard Diet during Unpredictable Chronic Mild Stress (UCMS)

Background. Anxiety and depression are becoming increasingly prevalent today and are often aggravated by day-to-day stresses. Because current management strategies are usually accompanied by unpleasant side effects, there is a need to look into alternative treatment regimens - such as prebiotics - that may provide equally effective anxiolytic and antidepressant effects. Objective. Therefore, the study aims to determine the effect of a combined fructooligosaccharide (FOS) and galactooligosaccharide (GOS) supplemented diet on anxiety and depression levels in mice subjected to Unpredictable Chronic Mild Stress (UCMS). Methods. Forty male BALB/C mice were subjected to UCMS under a pretest-posttest control group design where the treatment group received prebiotic supplementation throughout the study. Repeated measures ANOVA was run to evaluate between, within, and time interactions of the measured anxiety parameters using the light-dark box test, and depression parameter using the fur coat state assessment. Results. Results show that (1) the FOS + GOS treatment did not give the treatment group an advantage over the control group during UCMS, (2) both groups grew more anxious and depressed over time, and (3) the treatment group grew more anxious with time in relation to control in terms of the total time spent in the light side. Conclusion. These imply that the UCMS protocol was successful in inducing stress in mice, but the FOS + GOS regimen failed to provide anxiolytic and antidepressant effects on male BALB/C mice exposed to UCMS.

Jie-Yu-He-Huan Capsule Ameliorates Anxiety-Like Behaviours in Rats Exposed to Chronic Restraint Stress via the cAMP/PKA/CREB/BDNF Signalling Pathway.

Chronic stress is a critical factor in the aetiology of anxiety disorders; however, in the clinic, enduring and preventive measures are not available, and therapeutic drugs are associated with inevitable side effects. Our study established an anxiety rat model using chronic restraint stress (CRS) and assessed these animals using the open-field test, elevated plus-maze test, and light-dark box test. Jie-Yu-He-Huan capsule (JYHH), a Chinese medicine formula, was used as a preventative drug. The HPA axis-mediated release of corticotropin-releasing hormone, adrenocorticotropic hormone, and corticosterone from the hypothalamus was tested. In the hippocampus and prefrontal cortex, concentrations of 5-HT and its metabolite 5-hydroxyindoleacetic acid, as well as monoamine oxidase A, glucocorticoid receptor, and 5-HT1A receptor expression levels, were measured. Furthermore, we examined protein and mRNA expression of cAMP-PKA-CREB-BDNF pathway components. The results showed that JYHH had a significant preventative effect on the anxiety-like behaviour induced by CRS and prevented abnormal changes in the HPA axis and 5-HT system. Furthermore, CRS inhibited the cAMP-PKA-CREB-BDNF pathway, which returned to normal levels following JYHH treatment. This might be the underlying molecular mechanism of the antianxiety effect of JYHH, which could provide a new clinical target for preventative anxiolytic drugs for chronic stress.

Neurochemical and Behavioral Effects of a New Hallucinogenic Compound 25B-NBOMe in Rats

4-Bromo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25B-NBOMe) is a hallucinogen exhibiting high binding affinity for 5-HT2A/C serotonin receptors. In the present work, we investigated its effect on dopamine (DA), serotonin (5-HT), acetylcholine (ACh), and glutamate release in the rat frontal cortex, striatum, and nucleus accumbens. Hallucinogenic activity, impact on cognitive and motor functions, and anxiogenic/anxiolytic properties of this compound were also tested. The release of DA, 5-HT, ACh, and glutamate was studied using microdialysis in freely moving animals. Hallucinogenic activity was investigated using head and body twitch response (WDS), cognitive functions were examined with the novel object recognition test (NOR), locomotor activity was studied in the open field (OF), while anxiogenic/anxiolytic effect was tested using the light/dark box (LDB). Neurotoxicity was evaluated with the comet assay. 25B-NBOMe increased DA, 5-HT, and glutamate release in all studied brain regions, induced hallucinogenic activity, and lowered the recognition index (Ri) vs. control in the NOR test. It also decreased locomotor activity of rats in the OF test. The effect of 25B-NBOMe in the NOR test was inhibited by scopolamine. In the LDB test, the time spent in the dark zone was longer in comparison to control and was dose-dependent. In contrast to MDMA, 25B-NBOMe showed subtle genotoxic effect observed in the comet assay.Our findings indicate that 25B-NBOMe shows hallucinogenic activity in the wide range of doses. The changes in neurotransmitter levels may be related to 25B-NBOMe affinity for 5-HT2A receptor. Alterations in the NOR, OF, and LDB indicate that 25B-NBOMe impacts short-term memory, locomotion, and may be anxiogenic.

Attenuation of Anxiety-Like Behavior by Helichrysum stoechas (L.) Moench Methanolic Extract through Up-Regulation of ERK Signaling Pathways in Noradrenergic Neurons.

The long-term use of anxiolytic and antidepressant drugs can cause a plethora of side effects and the use of complementary and alternative medicine, which is generally considered safer than conventional medicine, is consistently increasing. Helichrysum stoechas (L.) Moench methanolic extract (HSE) has shown MAO-A inhibitory properties in previous studies. With the aim of obtaining innovative and safer therapies for mood disorders, this study investigated the potential activity of HSE in the management of anxiety- and depression-related symptoms. HSE showed dose-dependent (30–100 mg/kg p.o.) anxiolytic-like activity in the light dark box and marble burying tests, without any antidepressant-like activity, as shown by the results of the tail suspension test. Additionally, HSE did not have any effect on the modulation of pain, which highlights its selectivity in the control of anxiety-related behavior. At active doses, HSE did not produce any sedative effect or result in impaired motor coordination and memory functions. Western blotting experiments showed the ability of HSE to counteract the reduction in the phosphorylation of ERK44/42, to restore brain-derived neurotrophic factor (BDNF) expression and to return cyclic AMP response element binding (CREB) levels to basal levels in noradrenergic hippocampal neurons of mice exposed to an anxiety-related environment, which indicates a protective role against anxiety behavior. These results suggest that oral administration of HSE might represent an interesting opportunity for the management of anxiety disorders.

Meta-analysis of cognitive and behavioral tests in leptin- and leptin receptor-deficient mice

Leptin is a hormone produced by adipocytes that regulates food intake and metabolism. Leptin-related gene-deficient mice, such as db/db and ob/ob mice, are widely used to study diabetes and its related diseases. However, broad effects of leptin appear to cause variability in behavioral test results. We performed a meta-analysis of major behavioral tests in db/db and ob/ob mice. These mice exhibited significant impairments in the Morris water maze, forced swim, novel object recognition, Y-maze, tail suspension, and light-dark box tests, whereas the elevated plus maze and open field tests did not reveal significant changes. We also performed correlation and regression analyses between the animals’ performances and the experimental protocols and conditions. The memory-related tests were characterized by the correlations of their results with animal age, while the performances in the elevated plus-maze and forced swim tests were affected by the width of the devices used. In conclusion, db/db and ob/ob mice mainly exhibit memory deficits and depression-like behavior, although experimenters should be aware of animal age and device size in conducting experiments.

Anxiolytic, Antidepressant-Like Proprieties and Impact on the Memory of the Hydro-Ethanolic Extract of Origanum majorana L. on Mice

Marjoram (Origanum majorana L.) infusion has been used as folk medicine against depression and anxiety. However, no studies have been carried out yet to prove those activities scientifically. In this study, the anxiolytic, antidepressant-like effects, and memory impact of the hydro-ethanolic extracts of marjoram were evaluated in mice. The hydro-ethanolic extracts (250 and 500 mg/kg) were evaluated for their central nervous effect using six different behavioral tests such as light–dark box (LDB) and open field (OF) for anxiety, forced swim test (FST), and tail suspension test (TST) for depression, and object recognition test (ORT), Morris water maze (MWM) for the impact on memory. The experiments were realized on days 1, 7, 14, and 21 of treatments and compared with bromazepam for anxiety (1 mg/kg) and paroxetine for depression (11.5 mg/kg). The phytochemical screening was performed by HPLC, and the acute and sub-acute toxicities were performed following OCED guidelines (N°423 and 407) with biochemical parameters evaluation and histopathological analysis. Oral administration of marjoram hydro-ethanolic extract induced significant anxiolytic and antidepressant-like effects without memory impairment, increasing the exploration and time spent in the light area in the LDB test in a similar way to that of bromazepam. In the FST and TST, the extract was as effective as paroxetine (11.5 mg/kg, p.o.) in reducing immobility. The phytochemical screening showed the presence of ferulic acid, naringin, hydroxytyrosol, geraniol, and quercetin. This study approves the traditional use of this plant and encourages further investigation on its bioactive compounds.

The effect of pectin of tansy, Tanacetum vulgare L., on anxiety and overeating food rich in fats and sugars in mice in modelling binge eating

Binge eating is repeated episodes of eating large amounts of sweet and fatty food in short periods. Dietary fibers, including pectin, significantly reduce the subjective ratings of hunger, and the amount of food eaten. However, studies showing the effect of dietary fibers on satiety use juices or yoghurts with added dietary fiber, or a kissel-like food. Thus, there is a lack of data on the effect of dietary fibres on binge eating of palatable food. The aim of the study was to assess the effect of tansy pectin on anxiety and the binge eating of palatable food in mice. Material and methods. 64 mice weighing 33.3±0.6 g were divided into two groups. Binge eating was induced in forty mice of the first group by consumption of sunflower halva (SH) in addition to regular chow for 24 h once a week. The total energy intake and separately the consumption of regular chow (RC) and SH were monitored. Tansy pectin in the form of an aqueous solution was administered to the mice using a gastric feeding tube (50 mg/kg body weight) before the last presentation of SH. Blood was obtained by cardiac puncture at the end of the last 24 h SH access period. The concentration of insulin and ghrelin in plasma samples were determined by the enzyme immunoassay. In animals of the second group, 24 hours after the administration of pectin, the level of anxiety and depression of mice was assayed with an open field test, a light-dark box test, an elevated plus-maze test, and a forced swim test. Throughout the study, water was used as a negative control, and imipramine at a dose of 20 mg/kg was used as a positive control. Results. Mice treated with tansy pectin ate 2.6 fold less SH within 3 h and 1.4 fold less within 24 h after oral administration of tansy pectin compared to control (water administration). Consumption of RC did not differ within 3 or 24 h. The total energy intake was 1.9 fold lower within 3 h in mice treated with tansy pectin. Within 24 h after pectin oral administration the total energy intake did not differ from control. Insulin plasma level was 2.5 fold lower and ghrelin plasma concentration was 25% higher in the mice that received pectin compared to control, at the end of the 24 h SH access period. The administration of tansy pectin was found to decrease anxietyrelated behaviour in mice. Its administration significantly increased the time spent in the central sector of the open field apparatus by 87%, the time spent in the light area of the light-dark box by 31%, and the time spent on the open arms of the elevated plus maze by 22% compared with the control. Conclusion. Overall, tansy pectin reduced the binge eating of SH representing highly palatable, sweet, and fatty food. Reduced intake SH lead to a decrease in insulin concentration. Blood level of ghrelin was increased in mice treated with tansy pectin at the end of the sweet and fatty food presentation period. Tansy pectin reduced the level of anxiety in mice.

Ventral pallidal GABAergic neurons control wakefulness associated with motivation through the ventral tegmental pathway

The ventral pallidum (VP) regulates motivation, drug addiction, and several behaviors that rely on heightened arousal. However, the role and underlying neural circuits of the VP in the control of wakefulness remain poorly understood. In the present study, we sought to elucidate the specific role of VP GABAergic neurons in controlling sleep–wake behaviors in mice. Fiber photometry revealed that the population activity of VP GABAergic neurons was increased during physiological transitions from non-rapid eye movement (non-REM, NREM) sleep to either wakefulness or REM sleep. Moreover, chemogenetic and optogenetic manipulations were leveraged to investigate a potential causal role of VP GABAergic neurons in initiating and/or maintaining arousal. In vivo optogenetic stimulation of VP GABAergic neurons innervating the ventral tegmental area (VTA) strongly promoted arousal via disinhibition of VTA dopaminergic neurons. Functional in vitro mapping revealed that VP GABAergic neurons, in principle, inhibited VTA GABAergic neurons but also inhibited VTA dopaminergic neurons. In addition, optogenetic stimulation of terminals of VP GABAergic neurons revealed that they promoted arousal by innervating the lateral hypothalamus, but not the mediodorsal thalamus or lateral habenula. The increased wakefulness chemogenetically evoked by VP GABAergic neuronal activation was completely abolished by pretreatment with dopaminergic D1 and D2/D3 receptor antagonists. Furthermore, activation of VP GABAergic neurons increased exploration time in both the open-field and light–dark box tests but did not modulate depression-like behaviors or food intake. Finally, chemogenetic inhibition of VP GABAergic neurons decreased arousal. Taken together, our findings indicate that VP GABAergic neurons are essential for arousal related to motivation.

Dysfunction of the serotonergic system in the brain of synapsin triple knockout mice is associated with behavioral abnormalities resembling synapsin-related human pathologies

Synapsins (Syns) are a family of phosphoproteins associated with synaptic vesicles (SVs). Their main function is to regulate neurotransmitter release by maintaining a reserve pool of SVs at the presynaptic terminal. Previous studies reported that the deletion of one or more Syn genes in mice results in an epileptic phenotype and autism-related behavioral abnormalities. Here we aimed at characterizing the behavioral phenotype and neurobiological correlates of the deletion of Syns in a Syn triple knockout (TKO) mouse model. Wild type (WT) and TKO mice were tested in the open field, novelty suppressed feeding, light-dark box, forced swim, tail suspension and three-chamber sociability tests. Using in vivo electrophysiology, we recorded the spontaneous activity of dorsal raphe nucleus (DRN) serotonin (5-HT) and ventral tegmental area (VTA) dopamine (DA) neurons. Levels of 5-HT and DA in the frontal cortex and hippocampus of WT and TKO mice were also assessed using a High-Performance Liquid Chromatography. TKO mice displayed hyperactivity and impaired social and anxiety-like behavior. Behavioral dysfunctions were accompanied by reduced firing activity of DRN 5-HT, but not VTA DA, neurons. TKO mice also showed increased responsiveness of DRN 5-HT-1A autoreceptors, measured as a reduced dose of the 5-HT-1A agonist 8-OH-DPAT necessary to inhibit DRN 5-HT firing activity by 50%. Finally, hippocampal 5-HT levels were lower in TKO than in WT mice. Overall, Syns deletion in mice leads to a reduction in DRN 5-HT firing activity and hippocampal 5-HT levels along with behavioral alterations reminiscent of human neuropsychiatric conditions associated with Syn dysfunction.

“We are antidepressant also”: aspirin and diclofenac sodium

Background: Many studies have indicated that inflammation and depression are associated with each other. Present study was taken up to prove antidepressant effect of aspirin and diclofenac sodium.Methods: The present study was divided into 6 phases with 5 groups of animals N=10. In study 1, C57Bl mice were used and in remaining 4 studies swiss albino mice. Amitriptyline was standard drug used. For each study first group of animals was treated with a saline solution 1ml P.O., and second group of animals injected with 0.1 ml of 2% formalin. In group 3, 4, 5 animals depression was produced by stressors and treated with aspirin 14mg/kg P.O., diclofenac sod. 10 mg/kg P.O. and amitriptyline 10 mg/kg P.O., respectively. Antidepressant activity of aspirin and diclofenac sodium was determined by using forced swim test, tail suspension test, elevated plus maze test and light dark box test. Inflammatory mediators (IL-6, TNF-α) and central neurotransmitters (5-HT, NE, Ach) were estimated.Results: In light dark box test, latency of first crossing, time spent in dark area were decreased and no. of crossing increased significantly in the aspirin, diclofenac sod. treated animals. In forced swim test, the immobility time was decreased. Swiss albino mice treated with aspirin, diclofenac sod. showed decreased concentration of IL-6 and TNF-α and increased concentration of serotonin, nor epinephrine and acetylcholine. In elevated plus maze test, no. of open arm, closed arm entries, time spent in open arm increased and time spent in closed arm decreased. In tail suspension test immobility time was decreased.Conclusions: Aspirin and diclofenac sodium has antidepressant activity.

Affective Disruption During Forced Ethanol Abstinence in C57BL/6J and C57BL/6NJ Mice.

In alcohol-dependent individuals, acute alcohol withdrawal results in severe physiological disruption, including potentially lethal central nervous system hyperexcitability. Although benzodiazepines successfully mitigate such symptoms, this treatment does not significantly reduce recidivism rates in postdependent individuals. Instead, persistent affective disturbances that often emerge weeks to months after initial detoxification appear to play a significant role in relapse risk; however, it remains unclear whether genetic predispositions contribute to their emergence, severity, and/or duration. Interestingly, significant genotypic and phenotypic differences have been observed among distinct C57BL/6 (B6) substrains, and, in particular, C57BL/6J (B6J) mice have been found to reliably exhibit higher voluntary ethanol (EtOH) intake and EtOH preference compared to several C57BL/6N (B6N)-derived substrains. To date, however, B6 substrains have not been directly compared on measures of acute withdrawal severity or affective-behavioral disruption during extended abstinence. Male and female B6J and B6NJ mice were exposed to either a 7-day chronic intermittent EtOH vapor (CIE) protocol or to ordinary room air in inhalation chambers. Subsequently, blood EtOH concentrations and handling-induced convulsions were evaluated during acute withdrawal, and mice were then tested weekly for affective behavior on the sucrose preference test, light-dark box test, and forced swim test throughout 4weeks of (forced) abstinence. Despite documented differences in voluntary EtOH intake between these substrains, we found little evidence for substrain differences in either acute withdrawal or long-term abstinence between B6J and B6NJ mice. In B6J and B6NJ mice, both the acute and long-term sequelae of EtOH withdrawal are dependent on largely nonoverlapping gene networks relative to those underlying voluntary EtOH drinking.

Chronic Voluntary Binge Ethanol Consumption Causes Sex-Specific Differences in Microglial Signaling Pathways and Withdrawal-associated Behaviors in Mice.

Microglia are the resident immune cells in the brain where they play essential roles in the development and maintenance of physiological functions of this organ. Aberrant activation of microglia is speculated to be involved in the pathogenesis of a variety of neurological disorders, including alcohol use disorders. Repeated binge ethanol (EtOH) consumption can have a profound impact on the function and integrity of the brain resulting in changes in behaviors such as withdrawal and reward. However, the microglial molecular and cellular pathways associated with EtOH binge consumption remain poorly understood. In this study, adult C57BL/6J male and female mice were subjected daily to a gelatin-based drinking-in-the-dark voluntary EtOH consumption paradigm (3h/d for 4months) to characterize EtOH consumption and withdrawal-associated and anxiety-like behaviors. Brain microglia were isolated at the end and analyzed for protein expression profile changes using unbiased mass spectrometry-based proteomic analysis. Both male and female mice consistently consumed binge quantities of EtOH daily, resulting in blood EtOH levels>80mg/dl measured at the end of the 3-hour daily consumption period. Although female mice consumed a significantly greater amount of EtOH than male mice, EtOH withdrawal-associated anxiety-like behaviors measured by marble-burying, light-dark box, and elevated plus maze tests were predominantly observed in male mice. Proteomic analysis of microglia isolated from the brains of animals at the end of the 4-month binge EtOH consumption identified 117 and 37 proteins that were significantly up- or downregulated in EtOH-exposed male and female mice, respectively, compared to their pair-fed controls. Protein expression profile-based pathway analysis identified several cellular pathways that may underlie the sex-specific and EtOH withdrawal-associated behavioral abnormalities. Taken together, our findings revealed sex-specific changes in EtOH withdrawal-associated behaviors and signaling pathways in the mouse brain microglia and may help advance our understanding of the molecular, cellular, and behavioral changes related to human binge EtOH consumption.

Hesperidin alleviates chronic restraint stress and lipopolysaccharide-induced Hippocampus and Frontal cortex damage in mice: Role of TLR4/NF-κB, p38 MAPK/JNK, Nrf2/ARE signaling

Stress and lipopolysaccharide (LPS) animal models are used for screening antidepressants and anxiolytic drugs. However, the lacunae for their combination (Restraint stress; RS and LPS) impacting inflammation, apoptosis and antioxidant signaling have not been explored. The present study investigated RS + LPS-induced neurobehavioral and neurochemical anomalies in hippocampus (HIP) and frontal cortex (FC) of mice. Furthermore, citrus-derived flavanone glycoside (Hesperidin; HSP) neuroprotective ability was also confirmed in this model. Male Balb/c mice were given RS (for 28 days) and LPS (single dose, 0.83 mg/kg, i.p.) on 28th day. RS + LPS challenge caused neurobehavioral deficits in mice as evaluated over elevated plus maze (EPM), open field test (OFT), light-dark box test, tail suspension test (TST), forced swim test (FST), sucrose preference test (SPT). Moreover, RS + LPS caused alteration via enhanced oxido-nitrosative stress, proinflammatory cytokines level (serum, HIP, FC), lower antioxidants (GSH, SOD, CAT), increased IBA-1, GFAP, TLR4/NF-κB, p38MAPK/JNK while decreased Nrf2/BDNF/HO-1 expression in HIP and FC of mice. The 21 days (8–28th day), HSP (50 and 100 mg/kg, p.o.) treatment significantly alleviated the anxiety and depressive-like behavior and reversed neurochemical, histopathological changes. HSP exerted the neuroprotective effect via its anti-inflammatory, anti-apoptotic, antioxidant and neurogenesis potential in treating psychiatric illness alone or associated with other diseases.

Perinatal fluoxetine treatment promotes long-term behavioral changes in adult mice.

Serotonin exerts a significant role in the mammalian central nervous system embryogenesis and brain ontogeny. Therefore, we investigate the effect of perinatal fluoxetine (FLX), a selective serotonin reuptake inhibitor, administration on the behavioral expression of adult male Swiss mice. For this purpose, two groups (n = 6 each, and ~ 35g) of pregnant female Swiss mice were mated. Their offspring were treated with FLX (10mg/Kg, s.c.) from postnatal day (PND) 5 to 15. At PND 16, one male puppy of each litter was euthanized, and the hippocampus was dissected for RNA analysis. At 70days of life, the male offspring underwent a behavioral assessment in the open field, object recognition task, light-dark box, tail suspension and rotarod test. According to our results, the programmed animals had a decrease in TPH2, 5HT1a, SERT, BDNF, and LMX1B expression. Also, it was observed less time of immobility in tail suspension test and higher grooming time in the open field test. In the light-dark box test, the FLX-treated offspring had less time in the light side than control. We also observed a low cognitive performance in the object recognition task and poor motor skill learning in the rotarod test. These findings suggest that programming with FLX during the neonatal period alters a hippocampal serotonergic system, promoting anxiety and antidepressant behavior in adults, as well as a low mnemonic capacity.

Environmental enrichment during adolescence heightens ethanol intake in female, but not male, adolescent rats that are selectively bred for high and low ethanol intake during adolescence

ABSTRACT Background: Discriminating between adolescents who will eventually have ethanol use problems from those who do not is important. Environmental enrichment is a promising approach to reduce drug-related problems, but its impact on ethanol’s effects and intake is being scrutinized. Objective: We tested the effects of environmental enrichment on ethanol intake, preference, and anxiety-like response as well as shelter seeking and risk-taking behaviors. Methods: Experiment 1 examined ethanol intake, preference, and anxiety-like responses in 46 male and 54 female Wistar rats that were derived from a short-term breeding program that selected for high and low ethanol drinking during adolescence (ADHI2 and ADLO2 lines, respectively). Shelter-seeking and risk-taking behaviors were assessed (Experiment 2) in ADHI2 and ADLO2 rats (73 males, 76 females) reared under environmental enrichment or standard housing conditions and given doses of ethanol (2.5 g/kg, intraperitoneal) for 3 weeks. Environmental enrichment was applied on postnatal days 21–42. Ethanol intake was measured on postnatal days 42–68. Anxiety-like behavior and exploratory responses were assessed using the light-dark box and multivariate concentric square field test. Results: In Experiment 1, environmental enrichment increased ethanol intake in female, but not male, ADHI2 and ADLO2 rats (p < 0.05). In the baseline measurement of Experiment 2, ADHI2 rats exhibited reduced risk-taking and increased anxiety-like behavior (p < .05). After exposure to environmental enrichment the ADHI and ADLO rats, both males and females, exhibited increased risk-taking and exploratory behavior (p < 0.05). Conclusions: Environmental enrichment appears to increase ethanol intake in female rats by promoting the exploration of new environments or stimuli. The findings indicate that environmental enrichment increased ethanol intake in female, but not male, rats. Clinical programs that treat alcohol use disorder by emphasizing environmental stimulation should be designed with caution.

Vitexin Possesses Anticonvulsant and Anxiolytic-Like Effects in Murine Animal Models.

Different types of epilepsy and forms of pathological anxiety have been described as significant neurological disorders that may exist as comorbidities. Some of those disorders share the association of affected limbic areas/neuropathological triggers as well as the use of drugs for their clinical management. The aim of this work was to investigate the anticonvulsant and anxiolytic properties of the vitexin (apigenin-8-C-glucoside), since this compound is a flavonoid usually found as one of the major constituents in several medicinal plants claimed as anxiolytics and/or anticonvulsants. This investigation was performed by the use of a series of classical murine animal models of chemically induced-seizures and of anxiety-related tests (open-field, elevated plus-maze, and light-dark box tests). Here, we show that the systemic administration of vitexin (1.25; 2.5 and 5 mg/kg; i.p.) exhibited selective protection against chemically-induced seizures. Vitexin did not block seizures evoked by glutamate receptors agonists (NMDA and kainic acid), and it did not interfere with the latencies for these seizures. Conversely, the same treatments protected the animals in a dose-dependent manner against the seizures evoked by the Gabaergic antagonists picrotoxin and PTZ and rise the latency time for the first seizure on non-protected animals. The higher dose of vitexin protected 100% of animals against the tonic-clonic seizures triggered by GABA antagonists. The results from open-field, elevated plus-maze, and light-dark box tests indicated the anxiolytic properties of vitexin at similar range of doses described for the anticonvulsant action screening. Furthermore, these results pointed that vitexin did not cause sedation or locomotor impairment on animals. The selective action of vitexin against picrotoxin and PTZ may reinforce the hypothesis by which this compound acts mainly by the modulation of GABAergic neurotransmission and/or related pathways. This could be useful to explain the dual activity of vitexin as anticonvulsant and anxiolytic, and highlight the pharmacological interest on this promising flavonoid.

Vendor differences in anxiety-like behaviors in female and male Sprague Dawley rats

Although Sprague Dawley outbred rats are commonly used in behavioral, physiological, and pharmacological studies, dramatic differences in responses may emerge from rats obtained from different suppliers even when sex, age, and environmental conditions are maintained constant. In the present study, we compared behavioral responses on three tests related to anxiety of Sprague Dawley female and male rats obtained from three different vendors in the United States: Charles River, Envigo, and Taconic. All rats were tested in the open field, light-dark box, and elevated zero maze. We found reduced time spent in the center area of the open field and decreased light compartment duration in the light-dark box test in female and male rats from Taconic compared to Charles River and Envigo rats, suggesting anxiety-like behaviors differ between the three vendors. No vendor differences were found on performance in the elevated zero maze. Furthermore, the contribution of stress hormones to vendor differences was examined by measuring serum corticosterone levels in rats 30 min after exposure to the elevated zero maze. There were no vendor differences in corticosterone levels, suggesting that endogenous levels of stress hormones most likely did not contribute to vendor differences in anxiety-like behaviors. Collectively, these findings highlight the importance of vendor selection of the Sprague Dawley stock for research involving behavioral tests related to anxiety.