Pharmacology Biochemistry and Behavior最新文献

{"title":"mGlu2 and mGlu3 receptor negative allosteric modulators attenuate the interoceptive effects of alcohol in male and female rats","authors":"Ryan E. Tyler ,&nbsp;Kalynn Van Voorhies ,&nbsp;Bruce E. Blough ,&nbsp;Antonio Landavazo ,&nbsp;Joyce Besheer","doi":"10.1016/j.pbb.2024.173767","DOIUrl":"https://doi.org/10.1016/j.pbb.2024.173767","url":null,"abstract":"<div><h3>Rationale</h3><p>The subjective effects of alcohol are associated with alcohol use disorder (AUD) vulnerability and treatment outcomes. The interoceptive effects of alcohol are part of these subjective effects and can be measured in animal models using drug discrimination procedures. The newly developed mGlu₂ and mGlu₃ negative allosteric modulators (NAMs) are potential therapeutics for AUD and may alter interoceptive sensitivity to alcohol.</p></div><div><h3>Objectives</h3><p>To determine the effects of mGlu₂ and mGlu₃ NAMs on the interoceptive effects of alcohol in rats.</p></div><div><h3>Methods</h3><p>Long-Evans rats were trained to discriminate the interoceptive stimulus effects of alcohol (2.0 g/kg, i.g.) from water using both operant (males only) and Pavlovian (male and female) drug discrimination techniques. Following acquisition training, an alcohol dose-response (0, 0.5, 1.0, 2.0 g/kg) experiment was conducted to confirm stimulus control over behavior. Next, to test the involvement of mGlu₂ and mGlu₃, rats were pretreated with the mGlu₂-NAM (VU6001966; 0, 3, 6, 12 mg/kg, i.p.) or the mGlu₃-NAM (VU6010572; 0, 3, 6, 12 mg/kg, i.p.) before alcohol administration (2.0 g/kg, i.g.).</p></div><div><h3>Results</h3><p>In Pavlovian discrimination, male rats showed greater interoceptive sensitivity to 1.0 and 2.0 g/kg alcohol compared to female rats. Both mGlu₂-NAM and mGlu₃-NAM attenuated the interoceptive effects of alcohol in male and female rats using Pavlovian and operant discrimination. There may be a potential sex difference in response to the mGlu₂-NAM at the highest dose tested.</p></div><div><h3>Conclusions</h3><p>Male rats may be more sensitive to the interoceptive effects of the 2.0 g/kg alcohol training dose compared to female rats. Both mGlu₂_-and mGlu₃_-NAM attenuate the interoceptive effects of alcohol in male and female rats. These drugs may have potential for treatment of AUD in part by blunting the subjective effects of alcohol.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140555713","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":"Unlocking the age-old secrets of reward and substance use","authors":"Che Liu,&nbsp;Francesca M. Filbey","doi":"10.1016/j.pbb.2024.173766","DOIUrl":"https://doi.org/10.1016/j.pbb.2024.173766","url":null,"abstract":"<div><p>Although substance use is widespread across the lifespan from early adolescence to older adulthood, the prevalence of substance use disorder (SUD) differs between age groups. These age differences in SUD rates necessitate an investigation into how age moderates reward sensitivity, and consequently influences the risks and consequences related to substance use. This theoretical review integrates evidence from the literature to address the dynamic interplay between age and reward in the context of substance use. Overall, increasing evidence demonstrates that age moderates reward sensitivity and underlying reward system neurobiology. Reward sensitivity undergoes a non-linear trajectory across the lifespan. Low levels of reward sensitivity are associated with childhood and late adulthood. In contrast, high levels are associated with early to late adolescence, followed by a decline in the twenties. These fluctuations in reward sensitivity across the lifespan contribute to complex associations with substance use. This lends support to adolescence and young adulthood as vulnerable periods for the risk of subsequent SUD. More empirical research is needed to investigate reward sensitivity during SUD maintenance and recovery. Future research should also involve larger sample sizes and encompass a broader range of age groups, including older adults.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140558914","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":"Inflammation and Connexin 43 profiles in the prefrontal cortex are relevant to stress susceptibility and resilience in mice","authors":"Hong Jiang ,&nbsp;Meng Zhang ,&nbsp;Hui-Qin Wang ,&nbsp;Ning-Ning Zhang ,&nbsp;Xin-Mu Li ,&nbsp;Xue-Ying Yang ,&nbsp;Ai-Ping Chen ,&nbsp;Xu Yan ,&nbsp;Zhao Zhang ,&nbsp;Shi-Feng Chu ,&nbsp;Zhen-Zhen Wang ,&nbsp;Nai-Hong Chen","doi":"10.1016/j.pbb.2024.173757","DOIUrl":"https://doi.org/10.1016/j.pbb.2024.173757","url":null,"abstract":"<div><p>Depression is a major chronic mental illness worldwide, characterized by anhedonia and pessimism. Exposed to the same stressful stimuli, some people behave normally, while others exhibit negative behaviors and psychology. The exact molecular mechanisms linking stress-induced depressive susceptibility and resilience remain unclear. Connexin 43 (Cx43) forms gap junction channels between the astrocytes, acting as a crucial role in the pathogenesis of depression. Cx43 dysfunction could lead to depressive behaviors, and depression down-regulates the expression of Cx43 in the prefrontal cortex (PFC). Besides, accumulating evidence indicates that inflammation is one of the most common pathological features of the central nervous system dysfunction. However, the roles of Cx43 and peripheral inflammation in stress-susceptible and stress-resilient individuals have rarely been investigated. Thus, animals were classified into the chronic unpredictable stress (CUS)-susceptible group and the CUS-resilient group based on the performance of behavioral tests following the CUS protocol in this study. The protein expression of Cx43 in the PFC, the Cx43 functional changes in the PFC, and the expression levels including interleukin (IL)-1β, tumor necrosis factor-α, IL-6, IL-2, IL-10, and IL-18 in the peripheral serum were detected. Here, we found that stress exposure triggered a significant reduction in Cx43 protein expression in the CUS-susceptible mice but not in the CUS-resilient mice accompanied by various Cx43 phosphorylation expression and the changes of inflammatory signals. Stress resilience is associated with Cx43 in the PFC and fluctuation in inflammatory signaling, showing that therapeutic targeting of these pathways might promote stress resilience.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140549395","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":"Limited bedding and nesting increases ethanol drinking in female rats","authors":"B.J. Parks,&nbsp;P. Salazar,&nbsp;L. Morrison,&nbsp;M.K. McGraw,&nbsp;M. Gunnell,&nbsp;J. Tobacyk,&nbsp;L.K. Brents,&nbsp;M.D. Berquist","doi":"10.1016/j.pbb.2024.173756","DOIUrl":"10.1016/j.pbb.2024.173756","url":null,"abstract":"<div><p>Prenatal opioid exposure (POE) and postnatal adverse experiences are early life adversities (ELA) that often co-occur and increase problematic alcohol (EtOH) drinking during adolescence. We investigated the relationship between POE, postnatal adversity, and adolescent EtOH drinking in rats. We also sought to determine whether ELAs affect alpha-adrenoceptor density in the brain because the noradrenergic system is involved in problematic alcohol drinking and its treatment. We hypothesized that the combination of POE and postnatal adversity will increase alcohol drinking in rats compared to rats with exposure to either adversity alone or to control. We also predicted that POE and postnatal adversity would increase α₁-adrenoceptor density and decrease α₂-adrenoceptor density in brain to confer a stress-responsive phenotype. Pregnant rats received morphine (15 mg/kg/day) or saline via subcutaneous minipumps from gestational day 9 until birth. Limited bedding and nesting (LBN) procedures were introduced from postnatal day (PD) 3-11 to mimic early life adversity-scarcity. Offspring rats (PD 31-33) were given opportunities to drink EtOH (20 %, v/v) using intermittent-access, two-bottle choice (with water) procedures. Rats given access to EtOH were assigned into sub-groups that were injected with either yohimbine (1 mg/kg, ip) or vehicle (2 % DMSO, ip) 30 min prior to each EtOH access session to determine the effects of α₂-adrenoceptor inhibition on alcohol drinking. We harvested cortices, brainstems, and hypothalami from EtOH-naïve littermates on either PD 30 or PD 70 and conducted radioligand receptor binding assays to quantify α₁- and α₂-adrenoceptor densities. Contrary to our hypothesis, only LBN alone increased EtOH intake in female adolescent rats compared to female rats with POE. Neither POE nor LBN affected α₁- or α₂-adrenoceptor densities in the cortex, brainstem, or hypothalamus of early- or late-aged adolescent rats. These results suggest a complex interaction between ELA type and sex on alcohol drinking.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140330058","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":"Methamphetamine increases risky choice in rats, but only when magnitude and probability of reinforcement are manipulated within a session","authors":"Justin R. Yates ,&nbsp;Shreeukta Adhikari ,&nbsp;Rayah E. Bako ,&nbsp;Kevin L. Berling ,&nbsp;Maria R. Broderick ,&nbsp;Reuben Mains ,&nbsp;Bradley Zwick","doi":"10.1016/j.pbb.2024.173751","DOIUrl":"10.1016/j.pbb.2024.173751","url":null,"abstract":"<div><p>Risky choice is associated with maladaptive behaviors, particularly substance use disorders. Current animal models of risky choice are often confounded by other constructs like behavioral flexibility and suboptimal choice. The purpose of the current experiment was to determine if the psychostimulant methamphetamine, a drug whose popularity has increased in recent years, increases risky choice in an equivalent expected value (EEV) task. In the EEV task, rats are given a choice between two reinforcer alternatives that differ in magnitude and probability of delivery, but have equivalent expected value. Forty-eight Sprague Dawley rats were tested in three versions of the EEV task. In the first version of the EEV task, both reinforcer magnitude and probability were adjusted across blocks of trials for both alternatives. In the second and the third versions of the EEV task, reinforcer magnitude was held constant across each block of trials (either 1 vs. 2 pellets or 4 vs. 5 pellets). We found that male rats preferred the “riskier” option, except when reinforcer magnitudes were held constant at 4 and 5 pellets across each block of trials. Methamphetamine (0.5 mg/kg) increased preference for the risky option in both males and females, but only when both reinforcer magnitude and probability were manipulated across blocks of trials for each alternative. The current results demonstrate that both magnitude of reinforcement and probability of reinforcement interact to influence risky choice. Overall, this study provides additional support for using reinforcers with expected value to measure risky choice.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140318889","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":"Sleep and local field potential effect of the D2 receptor agonist bromocriptine during the estrus cycle and postpartum period in female rats","authors":"Attila Tóth ,&nbsp;Dóra Keserű ,&nbsp;Máté Pethő ,&nbsp;László Détári ,&nbsp;Norbert Bencsik ,&nbsp;Árpád Dobolyi ,&nbsp;Tünde Hajnik","doi":"10.1016/j.pbb.2024.173754","DOIUrl":"10.1016/j.pbb.2024.173754","url":null,"abstract":"<div><h3>Background</h3><p>Pituitary lactotrophs are under tonic dopaminergic inhibitory control and bromocriptine treatment blocks prolactin secretion.</p></div><div><h3>Methods</h3><p>Sleep and local field potential were addressed for 72 h after bromocriptine treatments applied during the different stages of the estrus cycle and for 24 h in the early- and middle postpartum period characterized by spontaneously different dynamics of prolactin release in female rats.</p></div><div><h3>Results</h3><p>Sleep changes showed strong dependency on the estrus cycle phase of the drug application. Strongest increase of wakefulness and reduction of slow wave sleep- and rapid eye movements sleep appeared during diestrus-proestrus and middle postpartum treatments.</p><p>Stronger sleep-wake effects appeared in the dark phase in case of the estrus cycle treatments, but in the light phase in postpartum treatments. Slow wave sleep and REM sleep loss in case of estrus cycle treatments was not compensated at all and sleep loss seen in the first day post-injection was gained further later. In opposition, slow wave sleep loss in the light phase after bromocriptine injections showed compensation in the postpartum period treatments.</p><p>Bromocriptine treatments resulted in a depression of local field potential delta power during slow wave sleep while an enhancement in beta and gamma power during wakefulness regardless of the treatment timing.</p></div><div><h3>Conclusions</h3><p>These results can be explained by the interplay of dopamine D2 receptor agonism, lack of prolactin release and the spontaneous homeostatic sleep drive being altered in the different stages of the estrus cycle and the postpartum period.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0091305724000480/pdfft?md5=e51d7cb16c57e558ba5656dc706e5aaa&pid=1-s2.0-S0091305724000480-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140306345","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":"Pentylenetetrazole kindling induces dynamic changes in GAD65 expression in hippocampal somatostatin interneurons","authors":"Yuki Kajita,&nbsp;Yuki Fukuda,&nbsp;Riho Kawamatsu,&nbsp;Takanori Oyanagi,&nbsp;Hajime Mushiake","doi":"10.1016/j.pbb.2024.173755","DOIUrl":"10.1016/j.pbb.2024.173755","url":null,"abstract":"<div><h3>Introduction</h3><p>One of the mechanisms of epileptgenesis is impairment of inhibitory neural circuits. Several studies have compared neural changes among subtypes of gamma-aminobutyric acid-related (GABAergic) neurons after acquired epileptic seizure. However, it is unclear that GABAergic neural modifications that occur during acquisition process of epileptic seizure.</p></div><div><h3>Methods</h3><p>Male rats were injected with pentylenetetrazole (PTZ kindling: <em>n</em> = 30) or saline (control: <em>n</em> = 15) every other day to observe the development of epileptic seizure stages. Two time points were identified: the point at which seizures were most difficult to induce, and the point at which seizures were most easy to induce. The expression of GABAergic neuron-related proteins in the hippocampus was immunohistochemically compared among GABAergic subtypes at each of these time points.</p></div><div><h3>Results</h3><p>Bimodal changes in seizure stages were observed in response to PTZ kindling. The increase of seizure stage was transiently suppressed after 8 or 10 injections, and then progressed again by the 16th injection. Based on these results, we defined 10 injections as a short-term injection period during which seizures are less likely to occur, and 20 injections as a long-term injection period during which continuous seizures are likely to occur. The immunohistochemical analysis showed that hippocampal glutamic acid decarboxylase 65 (GAD65) expression was increased after short-term kindling but unchanged after long-term kindling. Increased GAD65 expression was limited to somatostatin-positive (SOM⁺) cells among several GABAergic subtypes. By contrast, GAD, GABA, GABA_AR α1, GABA_BR1, and VGAT cells showed no change following short- or long-term PTZ kindling.</p></div><div><h3>Conclusion</h3><p>PTZ kindling induces bimodal changes in the epileptic seizure stage. Seizure stage is transiently suppressed after short-term PTZ injection with GAD65 upregulation in SOM⁺ cells. The seizure stage is progressed again after long-term PTZ injection with GAD65 reduction to baseline level.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0091305724000492/pdfft?md5=6c78cab6dc46f83ad326c44c9c0333d3&pid=1-s2.0-S0091305724000492-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140270463","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":"Editorial for the 50th anniversary of Pharmacology Biochemistry and Behavior","authors":"Guy Griebel","doi":"10.1016/j.pbb.2024.173753","DOIUrl":"10.1016/j.pbb.2024.173753","url":null,"abstract":"","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140207459","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":"Modulation of mGlu5 reduces rewarding associative properties of nicotine via changes in mesolimbic plasticity: Relevance to comorbid cigarette smoking in psychosis","authors":"Loren D. Peeters ,&nbsp;Liza J. Wills ,&nbsp;Anthony M. Cuozzo ,&nbsp;Kira L. Ivanich ,&nbsp;Seth E. Turney ,&nbsp;Luke P. Bullock ,&nbsp;Robert M. Price Jr ,&nbsp;Justin T. Gass ,&nbsp;Russell W. Brown","doi":"10.1016/j.pbb.2024.173752","DOIUrl":"10.1016/j.pbb.2024.173752","url":null,"abstract":"<div><h3>Rationale</h3><p>Antipsychotic medications that are used to treat psychosis are often limited in their efficacy by high rates of severe side effects. Treatment success in schizophrenia is further complicated by high rates of comorbid nicotine use. Dopamine D₂ heteroreceptor complexes have recently emerged as targets for the development of more efficacious pharmaceutical treatments for schizophrenia.</p></div><div><h3>Objective</h3><p>The current study sought to explore the use of the positive allosteric modulator of the mGlu5 receptor 3-Cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) as a treatment to reduce symptoms related to psychosis and comorbid nicotine use.</p></div><div><h3>Methods</h3><p>Neonatal treatment of animals with the dopamine D₂-like receptor agonist quinpirole (NQ) from postnatal day (P)1–21 produces a lifelong increase in D₂ receptor sensitivity, showing relevance to psychosis and comorbid tobacco use disorder. Following an 8-day conditioning paradigm, brain tissue in the mesolimbic pathway was analyzed for several plasticity markers, including brain derived neurotrophic factor (BDNF), phosphorylated p70 ribosomal S6 kinase (phospho-p70S6K), and cadherin-13 (Cdh13).</p></div><div><h3>Results</h3><p>Pretreatment with CDPPB was effective to block enhanced nicotine conditioned place preference observed in NQ-treated animals. Pretreatment was additionally effective to block the nicotine-induced increase in BDNF and sex-dependent increases in cadherin-13 in the ventral tegmental area (VTA), as well as increased phospho-p70S6K in the nucleus accumbens (NAcc) shell found in NQ-treated animals.</p></div><div><h3>Conclusion</h3><p>In conjunction with prior work, the current study suggests positive allosteric modulation of the mGlu5 receptor, an emerging target for schizophrenia therapeutics, may be effective for the treatment of comorbid nicotine abuse in psychosis.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140194391","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":"Running exercise improves astrocyte loss, morphological complexity and astrocyte-contacted synapses in the hippocampus of CUS-induced depression model mice","authors":"Yue Li ,&nbsp;Yanmin Luo ,&nbsp;Peilin Zhu ,&nbsp;Xin Liang ,&nbsp;Jing Li ,&nbsp;Xiaoyun Dou ,&nbsp;Li Liu ,&nbsp;Lu Qin ,&nbsp;Mei Zhou ,&nbsp;Yuhui Deng ,&nbsp;Lin Jiang ,&nbsp;Shun Wang ,&nbsp;Wenyu Yang ,&nbsp;Jing Tang ,&nbsp;Yong Tang","doi":"10.1016/j.pbb.2024.173750","DOIUrl":"10.1016/j.pbb.2024.173750","url":null,"abstract":"<div><p>Although the antidepressant effects of running exercise have been widely reported, further research is still needed to determine the structural bases for these effects. Astrocyte processes physically contact many synapses and directly regulate the numbers of synapses, but it remains unclear whether running exercise can modulate astrocyte morphological complexity and astrocyte-contacted synapses in the hippocampus of the mice with depressive-like behavior. Male C57BL/6 J mice underwent four weeks of running exercise after four weeks of chronic unpredictable stress (CUS). The sucrose preference test (SPT), tail suspension test (TST) and forced swim test (FST) were used to assess anhedonia in mice. Western blotting was used to measure the expression of astrocyte- and synapse-related proteins. Immunofluorescence and 3D reconstruction were used to quantify the density and morphology of astrocytes, and astrocyte-contacted synapses in each hippocampal subregion. Four weeks of running exercise alleviated depressive-like symptoms in mice. The expression of astrocyte- and synapse-related proteins in the hippocampus; astrocyte process lengths, process numbers, and dendritic arborization; and the number of astrocyte-contacted PSD95 positive synapses in the CA2–3 and DG regions were significantly decreased in the mice with depressive-like behavior, and running exercise successfully reserved these changes. Running exercise improved the decreases in astrocyte morphological complexity and astrocyte-contacted PSD95 positive synapses in the CA2–3 and DG regions of the mice with depressive-like behavior, suggesting that the physical interactions between astrocytes and synapses can be increased by running exercise, which might be an important structural basis for the antidepressant effects of running exercise.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143952","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}