Pharmacology Biochemistry and Behavior最新文献

{"title":"Re-socialization reduces social isolation-induced high alcohol preference and anxiety via possibly restoring dopamine-rewarding effects in the rat striatum","authors":"Lei An ,&nbsp;Yuxiu Xiong ,&nbsp;Yang Yang ,&nbsp;Dan Lyu ,&nbsp;Zhuo Yang ,&nbsp;Tao Zhang","doi":"10.1016/j.pbb.2025.173981","DOIUrl":"10.1016/j.pbb.2025.173981","url":null,"abstract":"<div><div>Social environmental factors frequently play an important role in early-life. It is reported that isolation increases vulnerability to develop alcohol use disorder. We investigated the effects of re-socialization on high alcohol preference and anxiety behaviors, induced by early-life social isolation (SI), and its possible underlying mechanism in male Wistar rats. On the 21st postnatal day, animals were either housed in groups of (CON) or isolated (SI-1) for the first stage (3 weeks). Afterwards, the SI-1 group were divided into two groups: re-socialization with socially housed rats (Re-SH) and isolation (SI-2) for a second stage (3 weeks). Both alcohol preference and behaviour tests were performed in these two stages. The ratio of dopamine content in striatum tissue was measured. The results showed that SI considerably induced the high alcohol preference and increased anxiety-like behaviors. However, during the 2nd stage, peer companionship significantly reduced the high alcohol preference and anxiety-like behaviors which were induced by early-life SI. Moreover, the striatal dopamine content was significantly enhanced by SI, but was evidently suppressed by re-socialization. Additionally, there was no statistical difference in body weight, anxiety-like behaviour, alcohol preference or dopamine content when the rats were only isolated during the SI-2 stage. It suggests that both the high alcohol preference and anxiety-like behaviors are able to be significantly reduced by re-socialization, which is possibly associated with regulating dopamine concentration.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"249 ","pages":"Article 173981"},"PeriodicalIF":3.3,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143478681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early-life stress of limited bedding/nesting material induced recognition memory loss and decreased hippocampal VGluT1 and nectin3 levels in aged male mice","authors":"Ze-Cong He ,&nbsp;Ya-Jie Yu ,&nbsp;Ting Wang ,&nbsp;Hui-Rong Yin ,&nbsp;Ya-Xin Sun ,&nbsp;Xiao Liu ,&nbsp;Xiao-Meng Xie ,&nbsp;Hong-Li Wang ,&nbsp;Yun-Ai Su ,&nbsp;Ji-Tao Li ,&nbsp;Tian-Mei Si","doi":"10.1016/j.pbb.2025.173980","DOIUrl":"10.1016/j.pbb.2025.173980","url":null,"abstract":"<div><div>Exposure to early-life stress has been found to lead to enduring psychiatric symptoms, including cognitive impairments that persist into adulthood and even old age. In this study, we investigated the behavioral effects and molecular changes of a well-established animal model of early-life stress, the limited bedding and nesting (LBN) model, in aged male mice. After 16 months, stressed mice showed a marked impairment in novel and spatial object recognition tasks, but not in temporal order memory or spatial working memory in the Y-maze spontaneous alternation task. These cognitive deficits were accompanied by a reduction in VGluT1 expression and a lower VGluT1/VGAT ratio in the CA1 region of the hippocampus, as well as reduced nectin3 expression in the mouse hippocampus. No significant molecular alterations were observed in the medial prefrontal cortex. These data support the notion that early-life stress leads to cognitive impairments in aged male mice, and these effects may be associated with a dysregulated excitatory/inhibitory balance and reduced nectin3 levels in the hippocampus.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"249 ","pages":"Article 173980"},"PeriodicalIF":3.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143479528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short-chain fatty acids in Huntington's disease: Mechanisms of action and their therapeutic implications","authors":"Mohamed J. Saadh ,&nbsp;Hanan Hassan Ahmed ,&nbsp;Radhwan Abdul Kareem ,&nbsp;Gaurav Sanghvi ,&nbsp;Subbulakshmi Ganesan ,&nbsp;Mohit Agarwal ,&nbsp;Parjinder Kaur ,&nbsp;Waam Mohammed Taher ,&nbsp;Mariem Alwan ,&nbsp;Mahmood Jasem Jawad ,&nbsp;Atheer Khdyair Hamad","doi":"10.1016/j.pbb.2025.173972","DOIUrl":"10.1016/j.pbb.2025.173972","url":null,"abstract":"<div><div>Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by motor dysfunction, cognitive decline, and emotional instability, primarily resulting from the abnormal accumulation of mutant huntingtin protein. Growing research highlights the role of intestinal microbiota and their metabolites, particularly short-chain fatty acids (SCFAs), in modulating HD progression. SCFAs, including acetate, propionate, and butyrate, are produced by gut bacteria through dietary fiber fermentation and are recognized for their neuroprotective properties. Evidence suggests that SCFAs regulate neuroinflammation, neuronal communication, and metabolic functions within the central nervous system (CNS). In HD, these compounds may support neuronal health, reduce oxidative stress, and enhance blood-brain barrier (BBB) integrity. Their mechanisms of action involve binding to G-protein-coupled receptors (GPCRs) and modulating gene expression through epigenetic pathways, underscoring their therapeutic potential. This analysis examines the significance of SCFAs in HD, emphasizing the gut-brain axis and the benefits of dietary interventions aimed at modifying gut microbiota composition and promoting SCFA production. Further research into these pathways may pave the way for novel HD management strategies and improved therapeutic outcomes.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"249 ","pages":"Article 173972"},"PeriodicalIF":3.3,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Purified cannabidiol leads to improvement of severe treatment-resistant behavioral symptoms in children with autism spectrum disorder","authors":"Pablo Sebastián Fortini ,&nbsp;Javier J. Toibaro ,&nbsp;Roberto H. Caraballo","doi":"10.1016/j.pbb.2025.173971","DOIUrl":"10.1016/j.pbb.2025.173971","url":null,"abstract":"<div><h3>Objective</h3><div>The aim of our study was to evaluate the efficacy and safety of purified cannabidiol as an add-on medication in pediatric patients with autism spectrum disorder (ASD) associated with treatment resistant repetitive behaviors, behavior disorders, and intellectual disability and unresponsive to conventional medications and behavioral interventions.</div></div><div><h3>Material and methods</h3><div>A prospective, observational, before-and-after study was conducted including 20 patients with severe ASD who initiated treatment with purified CBD. Patients were evaluated using different scales at baseline and at three-month intervals during followup.</div></div><div><h3>Results</h3><div>The median total CBD dose was 363.5 mg (range, 100–700), and the median follow-up was 11 months (range, 6–12). As to the primary outcome evaluating symptoms reported by parents, improvement in at least one was observed after CBD initiation in 18 patients (90 %) and no improvement in two (10 %) (1 worsening, 1 no response). In the responders, 83.5 % (<em>n</em> = 76) of all reported symptoms improved. Regarding the secondary outcomes based on the assessment with different scales, improvement of around 30 % was found in irritability, social withdrawal, hyperactivity. Restricted and repetitive behavior improved in nine (50 %), while no changes were seen in seven (38.8 %). Sleep patterns were found to be slightly improved. Adverse effects were reported in 13 patients (65 %), mainly consisting of increased irritability and decreased appetite, but were mild or moderate and transient in all. In 40 % of the children, concomitant medication could be reduced or partially discontinued.</div></div><div><h3>Conclusion</h3><div>Our results suggest that treatment with purified CBD is effective and safe and could benefit patients with severe ASD by improving some of the core symptoms, including repetitive behaviors and social interaction, as well as associated comorbidities. The families considered the quality of life to have improved.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"249 ","pages":"Article 173971"},"PeriodicalIF":3.3,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Striatal dopamine D2, adenosine A2A and cannabinoid CB1 receptors balance as a target against non-cognitive symptoms in a mouse model of Alzheimer's disease","authors":"Laura Gómez-Acero ,&nbsp;Nuria Sánchez-Fernández ,&nbsp;Paula Subirana ,&nbsp;Francisco Ciruela ,&nbsp;Ester Aso","doi":"10.1016/j.pbb.2025.173970","DOIUrl":"10.1016/j.pbb.2025.173970","url":null,"abstract":"<div><div>Behavioral and psychological symptoms of dementia are almost ubiquitous in Alzheimer's disease (AD) but current therapies are not fully effective and safe. In this study, we aim to evaluate the role played by the interplay among striatal D₂, adenosine A_2A (A_2AR) and cannabinoid CB₁ (CB₁R) receptors in some of these non-cognitive impairments in a well-established animal model of AD, the double transgenic APP/PS1 mice. Our results reveal that the alterations existing in the ratios between these three receptors significantly correlate with the sensorimotor gating and the social interaction impairments occurring in APP/PS1 mice at 12 months of age. Moreover, the pharmacological stimulation of A_2AR and CB₁R blunted the sensorimotor gating deficiencies in APP/PS1 mice. To note, we observed some age-dependent differences among male and female mice. In conclusion, the present study provides evidence for the contribution of an altered interplay between dopaminergic, adenosinergic and endocannabinoid systems in the sensorimotor gating deficits and social withdrawal occurring in AD and points to A_2AR and CB₁R as a potential target to reverse these non-cognitive symptoms in AD patients.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"249 ","pages":"Article 173970"},"PeriodicalIF":3.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age- and sex-dependent participation of the endocannabinoid system in locomotion and risk assessment of an ADHD rat model","authors":"Daniel Bussinger de Souza Penna ,&nbsp;Samara Gumiéro Costa ,&nbsp;Juliana Santos Romão ,&nbsp;Karin da Costa Calaza ,&nbsp;Karen de Jesus Oliveira ,&nbsp;Alexandre dos Santos Rodrigues ,&nbsp;Pablo Pandolfo","doi":"10.1016/j.pbb.2025.173969","DOIUrl":"10.1016/j.pbb.2025.173969","url":null,"abstract":"<div><div>Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder affecting individuals across age groups. Impairments in executive function characterize ADHD and are often associated with elevated levels of risk-taking behaviors. The endocannabinoid system plays a crucial role in modulating prefrontal cortex circuits. Here, we assessed the effects of acute pharmacological manipulation of cannabinoid CB1 and CB2 receptors on locomotion and risk assessment/anxiety-like behaviors in an ADHD animal model during adolescence and adulthood. Further, we investigated the protein levels and gene expression of endocannabinoid system components (CB1, CB2, FAAH, MAGL) in the prefrontal cortex at both ages. During adolescence, activation of cannabinoid receptors aggravated the hyperactivity and risky behaviors of the ADHD model. These behavioral traits were more evident in female rats. In adulthood, manipulation of cannabinoid receptors did not alter hyperactivity but worsened risk assessment. Overall, gene expression levels of receptors and enzymes of the endocannabinoid system were increased in the ADHD model. Our findings suggest that the endocannabinoid system may operate differently in ADHD, and manipulating this system, especially in adolescents, could exacerbate deficits in inhibitory control.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"248 ","pages":"Article 173969"},"PeriodicalIF":3.3,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabidiol interactions with oxycodone analgesia in an operant orofacial cutaneous thermal pain assay following oral administration in rats","authors":"Ariana C. Brice-Tutt ,&nbsp;Niall P. Murphy ,&nbsp;Barry Setlow ,&nbsp;Alexandria S. Senetra ,&nbsp;Wendi Malphurs ,&nbsp;Robert M. Caudle ,&nbsp;Adriaan W. Bruijnzeel ,&nbsp;Marcelo Febo ,&nbsp;Abhisheak Sharma ,&nbsp;John K. Neubert","doi":"10.1016/j.pbb.2025.173968","DOIUrl":"10.1016/j.pbb.2025.173968","url":null,"abstract":"<div><div>Previous studies have driven the notion that the cannabis constituent cannabidiol could be an effective adjunct to opioid administration for managing pain. Most of these studies have used experimental rodents with routes of administration, such as subcutaneous and intraperitoneal, that do not correspond with the routes used in clinical practice. In response to this, we tested the ability of cannabidiol co-administration to augment opioid analgesia via the more clinically-relevant oral route of administration. To this end, male and female rats were orally gavaged with cannabidiol (25 mg/kg), oxycodone (1.4 mg/kg), or a combination of both, after which they were tested in an operant thermal orofacial pain assay in which they voluntarily exposed their faces to cutaneous thermal pain to receive a palatable reward. All three drug conditions produced analgesic effects of varying degrees, being most profound in the combination group where a statistically significant enhancement over oxycodone-induced analgesia alone was evident. Additionally, oxycodone administration decreased lick frequencies – a measure of motor coordination of rhythmic movements - which too was magnified by co-administration of cannabidiol. Together these studies provide further support of an ability of cannabidiol to augment opioid effects, particularly analgesia, when administered by a route relevant to human pain management. As such, they encourage the notion that cannabidiol could find utility as an opioid-sparing approach to treating pain.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"250 ","pages":"Article 173968"},"PeriodicalIF":3.3,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination treatment with rapamycin and glucocorticoid protects the death of mesostriatal dopaminergic neurons in animal model of Parkinson's disease","authors":"Kina Lee ,&nbsp;Hee Jeong Kim ,&nbsp;Jeong Eun Kim ,&nbsp;K.C. Elina ,&nbsp;Sangjune Kim ,&nbsp;Young Seok Park ,&nbsp;Hyong Kyu Kim","doi":"10.1016/j.pbb.2025.173966","DOIUrl":"10.1016/j.pbb.2025.173966","url":null,"abstract":"<div><div>Glucocorticoids have been used to treat inflammatory diseases because of their potent anti-inflammatory and immunosuppressive actions. However, chronic use of high levels of glucocorticoids causes several adverse effects, limiting their clinical utility. Here, we explored the therapeutic potential of a combination treatment involving reduced concentrations of rapamycin, an autophagy activator and immunosuppressant, and glucocorticoids in an animal model of Parkinson's disease (PD). <em>In vitro</em> experiments with the SH-SY5Y cell line revealed that 10 μM rapamycin significantly increased the survival rate of cells treated with 6-hydroxydopamine to induce cell death, while both dexamethasone and prednisone at 50 μM exhibited an evident increase in survival rates. The combination treatment with reduced concentrations (rapamycin: 5 μM, dexamethasone: 25 μM) showed a more effective recovery in survival than singular treatments with high concentrations of rapamycin, prednisone, or dexamethasone. Propidium iodide–staining confirmed the efficacy of the combination treatment. This treatment did not significantly alter forkhead box O3a (FOXO3a)–triggered apoptosis and autophagic flux but upregulated the expression of the anti-apoptotic protein B-cell lymphoma 2, while B-cell lymphoma–extra-large showed no significant change. <em>In vivo</em> experiments using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)–induced PD animal model revealed that the combination treatment effectively mitigated defects in motor function. The combination treatment completely blocked the loss of tyrosine hydroxylase (TH)–positive neurons in the substantia nigra pars compacta and partially prevented the reduction of TH-positive fibers in the striatum caused by the MPTP treatment. It also reduced the microglial levels caused by the MPTP treatment. Although not significant, it demonstrated an increase in survival rates of MPTP-induced PD model mice. In conclusion, the combination treatment with reduced concentrations of rapamycin and glucocorticoids may serve as potential therapy for PD, albeit further research and clinical trials are warranted to validate its efficacy and safety.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"248 ","pages":"Article 173966"},"PeriodicalIF":3.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143142087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GW117 induces anxiolytic effects by improving hippocampal functions","authors":"Ya-qi Yang ,&nbsp;Murezati Tiliwaerde ,&nbsp;Na-na Gao ,&nbsp;Wei Gu ,&nbsp;Ting-ting Zhang ,&nbsp;Zeng-liang Jin","doi":"10.1016/j.pbb.2024.173927","DOIUrl":"10.1016/j.pbb.2024.173927","url":null,"abstract":"<div><div>GW117 functions as both an MT1/MT2 receptor agonist and a 5-HT2C receptor antagonist. This study aimed to investigate the anxiolytic effects of GW117 through behavioral assessments, including the open field test and novelty-suppressed feeding test (NSFT) within a chronic unpredictable mild stress (CUMS) model. GW117 was administered via oral gavage for 21 days to evaluate its sustained anxiolytic effects, with behavioral tests including the NSFT, the Vogel-conflict test, and the O-maze test. To explore the underlying mechanisms, we performed Western blot analyses to assess the expression levels of BCL2-Associated X (Bax), cleaved caspase-3, B-cell lymphoma-2 (Bcl-2), brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP). Additionally, BrdU labeling and immunofluorescence staining were used to examine changes in neuronal regeneration and astrocytogenesis. Our results demonstrated that GW117 produced significant anxiolytic effects across all behavioral assays, both in the CUMS model and during long-term administration. Mechanistic studies revealed that GW117 notably increased the expression of BDNF, GFAP, and Bcl-2, while reducing Bax and cleaved caspase-3 levels in the hippocampus of CUMS model rats. Furthermore, the populations of BrdU-positive and GFAP-positive cells were elevated. These findings suggest that GW117 exerts anxiolytic effects, potentially through enhancements in hippocampal function.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"247 ","pages":"Article 173927"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Caffeic acid differentially modulates behavior and neurochemicals in chronic unpredictable mild stress and dexamethasone induced models of depression","authors":"Hariom,&nbsp;Prerna Kumari,&nbsp;Sushma Chaturvedi,&nbsp;Sonika Shrivastav,&nbsp;Sushma Maratha,&nbsp;Vaibhav Walia","doi":"10.1016/j.pbb.2024.173930","DOIUrl":"10.1016/j.pbb.2024.173930","url":null,"abstract":"<div><div>In the present study authors studied the effect of caffeic acid (CA) in chronic unpredictable mild stress (CUMS) and dexamethasone (DEXA) model of depression. CUMS (21 days) and DEXA (1.5 mg/kg × 21 days) was used for the induction of depression and anxiety related behavior. Locomotor activity was determined using actophotometer. Depression related behavior was determined using tail suspension test (TST) and forced swim test (FST) whereas for the determination of anxiety related behavior elevated plus maze (EPM) test was used. Following behavioral studies, mice were sacrificed by decapitation method. Hippocampus was dissected and was used for the neurochemical assays including 5-HT (serotonin), glutamate, nitrite and gamma-aminobutyric acid (GABA). The results obtained suggested that the CA (25–100 mg/kg, i.p.) did not affect the activity count in CUMS exposed and DEXA treated mice. CA (50 mg/kg) evoked anxiogenic reactions in CUMS model by increasing the hippocampal nitrite and glutamate level while CA (50 mg/kg) exerted anxiolysis in DEXA model by reducing the level of 5-HT. In CUMS model, CA exerted antidepressant like effect by increasing the hippocampal nitric oxide (NO) level, in DEXA model CA exerted antidepressant like effect by reducing the hippocampal glutamate level. CA failed to reverse DEXA mediated nNOS inhibition and therefore decreases hippocampal glutamate level to exert antidepressant like effect. Thus, CA modulate anxiety and depression related neurobehavioral alterations in both CUMS and DEXA models.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"247 ","pages":"Article 173930"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}