Pharmacology Biochemistry and Behavior最新文献

{"title":"5-HT1B receptor activation produces rapid antidepressant-like effects in rodents","authors":"Erin A. Clark ,&nbsp;Lien Wang ,&nbsp;Taleen Hanania ,&nbsp;Karla Kretschmannova ,&nbsp;Massimiliano Bianchi ,&nbsp;Elizabeth Jagger ,&nbsp;Tingting Hu ,&nbsp;Fugang Li ,&nbsp;Yasir Gallero-Salas ,&nbsp;Kenneth S. Koblan ,&nbsp;Nina Dedic ,&nbsp;Linda J. Bristow","doi":"10.1016/j.pbb.2024.173917","DOIUrl":"10.1016/j.pbb.2024.173917","url":null,"abstract":"<div><div>Ketamine is noted for its rapid onset antidepressant response and effectiveness in patients with treatment resistant depression. While most research has focused on glutamatergic mechanisms, recent studies show that antidepressant-like effects in rodents are dependent upon the serotonergic (5-HT) system and suggest a potential contribution of the 5-HT_1B receptor. In this study we utilized CP-94253 to examine whether 5-HT_1B receptor agonism produces rapid and sustained antidepressant-like effects, focusing on rodent models and treatment approaches commonly used to demonstrate the differentiated response to ketamine. We first confirmed that CP-94253 is a potent 5-HT_1B agonist <em>in vitro</em> and that CP-94253 occupies brain 5-HT_1B receptors at the doses tested. CP-94253 reduced immobility in the mouse forced swim test (FST) and exhibited a prominent antidepressant signature in the mouse-behavior phenotyping platform SmartCube®. When examined 24 h after acute treatment, CP-94253 reduced FST immobility in both naïve rats and in rats receiving chronic interferon alpha treatment. <em>Ex vivo</em> hippocampal long-term potentiation was also enhanced in naïve rats receiving acute CP-94253 treatment, 24 h prior to the recordings. In mice exposed to chronic social defeat stress, antidepressant-like effects in the tail suspension and sucrose preference tests were seen 1 h and 24 h after acute treatment, respectively. Finally, whole brain c-fos imaging in mice showed that CP-94253 modulates neuronal activity in discrete brain regions including the lateral habenula circuit implicated in depression and the ketamine treatment response. Collectively these results support the further investigation of 5-HT_1B agonism as a novel treatment approach for major depressive disorder.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"247 ","pages":"Article 173917"},"PeriodicalIF":3.3,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751304","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":"Myelin Transcription Factor 1 (MyT1) overexpression mitigates social isolation-induced behavioral deficits: Insights into cortical synaptotagmin 1 regulation and antidepressant-like effects","authors":"Amine Bahi ,&nbsp;Jean-Luc Dreyer","doi":"10.1016/j.pbb.2024.173912","DOIUrl":"10.1016/j.pbb.2024.173912","url":null,"abstract":"<div><div>Social isolation (SI) stress is increasingly recognized as a concern, associated with detrimental effects on mood and emotional well-being. Myelin Transcription Factor 1 (MyT1) is known for its pivotal role in nervous system development and mood regulation. This study delves into the potential of MyT1 to mitigate SI-induced behavioral abnormalities in mice. Utilizing a chronic SI model involving neonatal and post-weaning SI, male and female mice were subjected to lentiviral overexpression of MyT1 specifically in the medial prefrontal cortex (mPFC). A battery of behavioral assessments, including novelty-suppressed feeding, sucrose preference, sucrose splash, tape grooming, tail suspension, and forced swim tests, revealed notable antidepressant-like effects in both sexes upon MyT1 overexpression. Enhanced MyT1 expression corresponded with increased feeding initiation, sucrose preference, and self-grooming, alongside decreased immobility time. Importantly, the upregulation of MyT1 was accompanied by a significant reduction in cortical synaptotagmin 1 (Syt1) level. These findings underscore the involvement of MyT1 in mitigating SI-induced depression-like behavior. Moreover, the observed alterations in behavior are closely associated with changes in cortical Syt1 expression, suggesting its potential role as a target for unraveling the molecular mechanisms underlying mood disorders induced by SI. This study sheds light on the intricate interplay between MyT1 and cortical function in modulating responses to SI, paving the way for potential therapeutic interventions targeting these pathways.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"246 ","pages":"Article 173912"},"PeriodicalIF":3.3,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731591","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":"Anxiety modulators elicit different behavioral outcomes in adult zebrafish: Emphasis on homebase-related parameters and spatio-temporal exploration","authors":"João V. Borba ,&nbsp;Cássio M. Resmim ,&nbsp;Falco L. Gonçalves ,&nbsp;Rossano M. Silva ,&nbsp;Camilla W. Pretzel ,&nbsp;Hevelyn S. Moraes ,&nbsp;Milena D. Sauter ,&nbsp;Denis B. Rosemberg","doi":"10.1016/j.pbb.2024.173914","DOIUrl":"10.1016/j.pbb.2024.173914","url":null,"abstract":"<div><div>Anxiety is an emotion that represents a crucial anticipatory reaction of aversive stimuli, with clinical relevance in cases of disproportional and severe occurrences. Although distinct animal models have contributed to elucidate anxiety-related mechanisms, the influence of anxiogenic and anxiolytic modulations on both locomotion and exploration-related parameters in the open field test (OFT) is not fully elucidated. Here, we aimed to assess the influence of anxiogenic and anxiolytic manipulations on the exploratory dynamics of adult zebrafish (<em>Danio rerio</em>) focusing on homebase-related behaviors. As anxiogenic manipulations, we used the morphine (1.5 mg/L) withdrawal protocol (MOR); 3.5 mL/L conspecific alarm substance (CAS) for 5 min; and 100 mg/L caffeine (CAF) for 15 min. To evoke anxiolytic-like responses, animals were acutely exposed to 0.5 % (<em>v</em>/v) ethanol (ETOH) for 1 h; 100 μg/L fluoxetine (FLU) for 15 min; and 0.006 mg/L clonazepam (CZP) for 10 min. Then, fish were individually exposed to the 30-min OFT trial, with posterior analysis of behavioral activity. While MOR induced hyperlocomotion and increased periphery occupancy, CAS and CAF groups showed higher immobility and increased latency to homebase formation, respectively. Conversely, ETOH and FLU reduced homebase occupancy, supporting anxiolytic-like behaviors, while CZP did not change zebrafish behavior in the OFT. Cluster analysis was used to reconfirm the remarkable similarities and discrepancies between treatments, thus contributing to characterize the distinct responses measured. Overall, our novel data show the relevance of homebase-related analysis as a sensitive tool to reflect affective-like states in zebrafish, providing innovative approaches to unravel the spatio-temporal dynamics of anxiety-like behaviors in vertebrates.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"246 ","pages":"Article 173914"},"PeriodicalIF":3.3,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710851","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":"The interaction effects between opioidergic and D1-like dopamine receptors in the nucleus accumbens on pain-related behaviors in the animal model of acute pain","authors":"Pariya Shahani ,&nbsp;Hedie Abolghasemi ,&nbsp;Shima Abtin ,&nbsp;Roghayeh Mozafari ,&nbsp;Nooshin Barikrow ,&nbsp;Batool Ghorbani Yekta ,&nbsp;Abbas Haghparast","doi":"10.1016/j.pbb.2024.173911","DOIUrl":"10.1016/j.pbb.2024.173911","url":null,"abstract":"<div><div>The opioidergic and dopaminergic systems play an essential role in processing pain information in the nucleus accumbens (NAc). The present work examined the hypothesis that interaction between opioidergic and D1-like dopamine receptors in the NAc area may influence acute pain-related behaviors. One hundred sixty adult male Wistar rats unilaterally received different doses of the drug solution or vehicle. First, separate groups of animals received different doses of morphine (5, 10, and 25 mmol/0.5 μL) and various doses of SKF38393 (1.5, 3, 6, and 12 mmol/0.5 μL) as opioid and D1-like receptor agonists in the NAc region, respectively. In the second set of experiments, animals got different amounts (1.5, 3, 6, and 12 mmol/0.5 μL) of SCH23390, a D1-like receptor antagonist, before an effective dose of morphine (10 mmol/0.5 μL). In the last experiment, the animals were given naloxone (1.5, 5, and 15 mmol/0.5 μL) before they were given an effective dose of SKF38393 (3 mmol/0.5 μL). The tail-flick test was then used to measure their acute pain threshold. The main findings showed that intra-NAc injection of morphine and SKF38393 alone causes antinociceptive responses. However, the intra-accumbal injection of SCH23390 significantly reduced the antinociceptive responses elicited by intra-NAc morphine. Additionally, intra-NAc naloxone significantly reduced the antinociceptive effects elicited by intra-NAc SKF38393. Interestingly, SCH23390 was more effective in reversing the analgesic effects of morphine (η2 = 0.61) than naloxone in reversing the analgesic effects of SKF38393 (η2 = 0.49). The findings suggest that the opioidergic and dopamine systems in the NAc collaborate to produce pain-relieving effects. This insight could potentially enhance the effectiveness of lower doses of opioids for pain management, ultimately reducing their usage in clinical settings in the future.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"246 ","pages":"Article 173911"},"PeriodicalIF":3.3,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715878","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":"Environmental enrichment attenuates maternal separation-induced excessive hoarding behavior in adult female mice","authors":"Yiming Cai ,&nbsp;Ruofan Zhao ,&nbsp;Yuxuan Huang ,&nbsp;Huiping Yang ,&nbsp;Ye Liu ,&nbsp;Rui Yang ,&nbsp;Xiangyu Zhang ,&nbsp;Yiran Liu ,&nbsp;Shu Yan ,&nbsp;Xiaoyu Liu ,&nbsp;Xiao Liu ,&nbsp;Xueyong Yin ,&nbsp;Yang Yu ,&nbsp;Shuai Gao ,&nbsp;Yating Li ,&nbsp;Ye Zhao ,&nbsp;Haishui Shi","doi":"10.1016/j.pbb.2024.173913","DOIUrl":"10.1016/j.pbb.2024.173913","url":null,"abstract":"<div><h3>Background</h3><div>Previous studies have demonstrated that early life stress (ELS) impacts hoarding behavior in adult humans. This study aimed to assess the potential mitigation by environmental enrichment on hoarding behavior in rodents caused by maternal separation, thereby providing insights into therapeutic strategies for hoarding disorder.</div></div><div><h3>Methods</h3><div>Newborn mice were randomly divided into four groups. The control group was allowed to grow naturally. The maternal separation group underwent two weeks of maternal separation. The short-term environmental enrichment group received two weeks of environmental enrichment intervention after the two weeks of maternal separation. The long-term environmental enrichment group received five weeks of environmental enrichment intervention after the two weeks of maternal separation. Hoarding behavior was assessed during adolescence and adulthood. Hippocampal tissue from adult female mice was analyzed using LC-MS/MS-based metabolomics. Spearman correlation analysis was then performed to assess the relationship between differentially expressed metabolites and hoarding behavior.</div></div><div><h3>Results</h3><div>Environmental enrichment attenuates maternal separation-induced excessive hoarding behavior in adult female mice. The untargeted metabolomics of the hippocampal region in female mice showed that long-term environmental enrichment reversed multiple differential metabolites, including Substance P, which were mainly concentrated in metabolic pathways such as cancer choline metabolism, glycolipid metabolism, and linoleic acid metabolism.</div></div><div><h3>Conclusions</h3><div>Our findings indicate that ELS and long-term environmental enrichment have sex-dependent effects on adult hoarding behavior, potentially related to altered hippocampal metabolism. This study highlights the importance of environmental enrichment in mitigating the long-term effects of early maternal separation on hoarding behavior.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"245 ","pages":"Article 173913"},"PeriodicalIF":3.3,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702662","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":"Repeated exposure to ethanol alters memory acquisition and neurotransmission parameters in zebrafish brain","authors":"Guilherme Lodetti ,&nbsp;Samira Leila Baldin ,&nbsp;Ana Carolina Salvador de Farias ,&nbsp;Karolyne de Pieri Pickler ,&nbsp;Amanda Gomes Teixeira ,&nbsp;Eduardo Ronconi Dondossola ,&nbsp;Henrique Teza Bernardo ,&nbsp;Caio Maximino ,&nbsp;Eduardo Pacheco Rico","doi":"10.1016/j.pbb.2024.173915","DOIUrl":"10.1016/j.pbb.2024.173915","url":null,"abstract":"<div><div>Alcohol is widely consumed worldwide and its abuse can cause cognitive dysfunction, affecting memory and learning due to several neurophysiological changes. An imbalance in several neurotransmitters, including the cholinergic and glutamatergic systems, have been implicated in these effects. Zebrafish are sensitive to alcohol, respond to reward stimuli, and tolerate and exhibit withdrawal behaviors. Therefore, we investigated the effects of repetitive exposure to ethanol (REE) and the NMDA receptor antagonist dizocilpine (MK-801) on memory acquisition and glutamatergic and cholinergic neurotransmission. Memory was assessed using the inhibitory avoidance and object recognition tasks. Brain glutamate levels and the activity of Na⁺-dependent transporters were evaluated as indexes of glutamatergic activity, while acetylcholinesterase (AChE) and choline acetyltransferase (ChAT), enzyme activity were evaluated as indexes of cholinergic activity. Behavioral assessments showed that REE impaired aversive and spatial memory, an effect that MK-801 mimicked. Glutamate levels, but not transporter activity, were significantly lower in the REE group; similarly, REE increased the activity of AChE, but not ChAT, activity. These findings suggest that intermittent exposure to ethanol leads to impairments in zebrafish memory consolidation, and that these effects could be associated with alterations in parameters related to neurotransmission systems mediated by glutamate and acetylcholine. These results provide a better understanding of the neurophysiological and behavioral changes caused by repetitive alcohol use.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"246 ","pages":"Article 173915"},"PeriodicalIF":3.3,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716864","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":"From colours to cravings: Exploring conditioned colour preference to ethanol in zebrafish","authors":"Ethan V. Hagen ,&nbsp;Yanbo Zhang ,&nbsp;Trevor J. Hamilton","doi":"10.1016/j.pbb.2024.173909","DOIUrl":"10.1016/j.pbb.2024.173909","url":null,"abstract":"<div><div>Conditioned preference paradigms like conditioned colour preference tests (CCP) can be used to investigate addictive drug seeking in zebrafish (<em>Danio rerio</em>), but many aspects of this procedure require further study. Conditioned preference can be tested with either biased or unbiased conditioning methods, each with their own strengths and weaknesses. The present study used unbiased stimuli to test seeking behaviour in ethanol-exposed zebrafish at different durations of drug withdrawal. Zebrafish were exposed to one of two equally preferred colours (red or yellow) while dosed with 0.8 % vol/vol ethanol or with habitat water (controls) for 1 h each day for 21 days. Next, fish experienced withdrawal for either 2-, 4-, or 8-days then were tested in a two-way red and yellow task for 10 min with their movement recorded via motion-tracking software. Fish conditioned to red showed a main effect of ethanol and a significant preference for red compared to yellow at 8-days of withdrawal but not at 2-days or 4-days of withdrawal. Fish conditioned to yellow did not show any colour preference during the 2-, 4-, or 8-days of withdrawal, but did show a main effect of withdrawal duration. This work expands our understanding of CCP paradigms in zebrafish and highlights the capacity of zebrafish to develop an association to red but not yellow under our experimental conditions.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"246 ","pages":"Article 173909"},"PeriodicalIF":3.3,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695753","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":"Dusting off old blueprints: Is it time to reconsider metabotropic glutamate receptor 2 for therapeutic drug development?","authors":"Anton Bespalov ,&nbsp;Robert Lütjens ,&nbsp;Dario Doller","doi":"10.1016/j.pbb.2024.173908","DOIUrl":"10.1016/j.pbb.2024.173908","url":null,"abstract":"<div><div>The metabotropic glutamate receptor 2 (mGlu₂) is a heavily studied therapeutic target in neuropsychiatry for which we anticipate a renewed interest in the near future. We review the rationale and the outcome of clinical trials with mGlu_2/3 receptor agonists in schizophrenia, a field of intense research since a seminal publication by Patel and colleagues (2007). We summarize evidence about selective, potent and safe agents with quantifiable CNS penetration that can be used to test hypotheses of mGlu₂ receptors involvement in neuropsychiatric diseases. We summarize lessons learned from previous programs that should be considered to maximize the probability of success when targeting orthosteric and allosteric enhancement of mGlu₂ receptor function in schizophrenia and beyond. First, we propose expanding our focus beyond presynaptic mGlu₂ receptor stimulation in schizophrenia to novel hypotheses and that the choice of a therapeutic indication no longer be dictated by commercial opportunity but following science as a driver. Second, evidence on internal validity of preclinical studies supporting efficacy claims in the mGlu₂ field is very limited. This gap will need to be closed when reviewing the rationale to re-initiate efforts in this field. Third, the pomaglumetad program was halted due to insufficient clinical efficacy, partly because of the inability to identify a treatment responder population. In preclinical studies, effects of mGlu_2/3 receptor stimulation also seemed to vary significantly between laboratories. Definition of the responsive subject population and development of response-predicting biomarkers is therefore one of the main avenues of further research in the mGlu₂ field.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"247 ","pages":"Article 173908"},"PeriodicalIF":3.3,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687578","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":"Conditioned place preference with low dose mixtures of α-pyrrolidinopentiophenone (α-PVP) and 3,4-methylenedioxypyrovalerone (MDPV) in male and female Sprague-Dawley rats","authors":"Jakob D. Shaykin,&nbsp;Lisa E. Baker","doi":"10.1016/j.pbb.2024.173907","DOIUrl":"10.1016/j.pbb.2024.173907","url":null,"abstract":"<div><div>Two common constituents of psychoactive “bath salts”, 3,4-methylenedioxypyrovalerone (MDPV) and α-pyrrolidinoipentiophenone (α-PVP) belong to a novel class of synthetic chemicals structurally related to the psychostimulant drug, cathinone. Recreational use of MDPV and α-PVP pose serious health risks, which may be exacerbated by concomitant use of both substances. Preclinical psychopharmacology studies have established that MDPV and α-PVP have high abuse liabilities, comparable to that of cocaine and methamphetamine. Whereas polysubstance use is common among recreational users of synthetic cathinones, preclinical behavioral assays can serve to inform potential behavioral health risks of drug mixtures. This study employed a rodent model of conditioned drug reward, conditioned place preference (CPP), to determine if concurrent treatment with MDPV (1 mg/kg) and α-PVP (1 mg/kg) produced stronger locomotor activation or CPP compared to each individual substance. A secondary aim of this study was to assess sex as variable in the behavioral effects of these substances. Females exhibited a stronger response than males to the locomotor stimulant effects of α-PVP and the α-PVP + MDPV mixture. Additionally, the α-PVP + MDPV mixture produced significantly greater increases in activity compared to either drug alone in females. MDPV and the α-PVP + MDPV mixture established CPP in both sexes, whereas α-PVP alone failed to produce CPP in either sex. These results are consistent with previous preclinical study findings that females may be more susceptible to the psychostimulant effects of these synthetic cathinones. Further investigation is warranted to determine the mechanisms responsible for sex differences in the behavioral effects of these drugs.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"245 ","pages":"Article 173907"},"PeriodicalIF":3.3,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676640","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":"Splenic γδ T cells mediate antidepressant and prophylactic actions of arketamine in lipopolysaccharide-induced depression in mice","authors":"Guilin Liu ,&nbsp;Li Ma ,&nbsp;Akemi Sakamoto ,&nbsp;Lisa Fujimura ,&nbsp;Dan Xu ,&nbsp;Mingming Zhao ,&nbsp;Xiayun Wan ,&nbsp;Rumi Murayama ,&nbsp;Naohiko Anzai ,&nbsp;Kenji Hashimoto","doi":"10.1016/j.pbb.2024.173906","DOIUrl":"10.1016/j.pbb.2024.173906","url":null,"abstract":"<div><div>Arketamine, the (<em>R</em>)-enantiomer of ketamine, exhibits both therapeutic and sustained prophylactic effects in an inflammation-driven model of depression, although the precise mechanisms remain elusive. Given the involvement of γδ T cells in inflammatory processes, this study explored their role in the effects of arketamine. To assess therapeutic outcomes, mice received lipopolysaccharide (LPS:1.0 mg/kg), followed by either arketamine (10 mg/kg) or saline. For prophylactic assessment, arketamine or saline was administered six days prior to LPS exposure. A single dose of LPS (1.0 mg/kg) reduced the proportion of γδ T cells in the spleen but did not affect their levels in the blood, prefrontal cortex, or small intestine. Arketamine mitigated LPS-induced splenomegaly, counteracted the elevation of plasma interleukin-6 levels and the reduction in the proportion of splenic γδ T cells, and alleviated depression-like behavior as assessed by the forced swimming test. Notably, negative correlations were observed between the proportion of splenic γδ T cells and indicators of inflammation and depression. Furthermore, pretreatment with a γδ TCR antibody significantly countered the therapeutic and prophylactic effects of arketamine on LPS-induced changes. These findings highlight a novel role for splenic γδ T cells in inflammation-associated depression and suggest the potential of arketamine as a treatment option. Consequently, γδ T cells may represent a novel therapeutic target for inflammation-related depression. Further studies on the role of γδ T cells in depressed patients with inflammation are warranted.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"245 ","pages":"Article 173906"},"PeriodicalIF":3.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644341","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}