Neuropharmacology最新文献

{"title":"Mild forced exercise in young mice prevents anergia induced by dopamine depletion in late adulthood: Relation to CDNF and DARPP-32 phosphorylation patterns in nucleus accumbens","authors":"Régulo Olivares-García ,&nbsp;Laura López-Cruz ,&nbsp;Carla Carratalá-Ros ,&nbsp;Paula Matas-Navarro ,&nbsp;John D. Salamone ,&nbsp;Mercè Correa","doi":"10.1016/j.neuropharm.2024.110197","DOIUrl":"10.1016/j.neuropharm.2024.110197","url":null,"abstract":"<div><div>Mesolimbic dopamine (DA) plays a critical role in behavioral activation and exertion of effort in motivated behaviors. DA antagonism and depletion in nucleus accumbens (Nacb) induces anergia in effort-based decision-making tasks. Exercise improves motor function in Parkinson's disease (PD). However, the beneficial effects of physical exercise on anergia, a symptom present in many psychiatric and neurological pathologies needs to be studied. During 9 weeks, young CD1 male mice were trained to run at a moderate speed in automatically turning running wheels (RW) (forced exercise group) or locked in static RWs (control group) in 1 h daily sessions. Both groups were tested in a 3-choice-T-maze task developed for the assessment of preference between active (RW) vs. sedentary reinforcers, and vulnerability to DA depletion-induced anergia was studied after tetrabenazine administration (TBZ; VMAT-2 blocker). Exercise did not change spontaneous preferences, did not affect body weight, plasma corticosterone levels or measures of anxiety, but it increased the cerebral DA neurotrophic factor (CDNF) in Nacb core, suggesting a neuroprotective effect in this nucleus. After TBZ administration, only the non-trained group showed a shift in relative preferences from active to sedentary options, reducing time running but increasing consumption of pellets, thus showing a typical anergic but not anhedonic effect. Moreover, only in the non-trained group, phosphorylation of DARPP-32(Thr34) increased after TBZ administration. These results are the first to show that mild forced exercise carried out from a young age to adulthood could act on Nacb-related functions, and prevent the anergia-inducing effects of DA depletion.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"262 ","pages":"Article 110197"},"PeriodicalIF":4.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"QRFP and GPR103 in the paraventricular nucleus play a role in chronic stress-induced depressive-like symptomatology by enhancing the hypothalamic-pituitary-adrenal axis","authors":"Yan-Mei Chen ,&nbsp;Jie Huang ,&nbsp;Hua Fan ,&nbsp;Wei-Yu Li ,&nbsp;Tian-Shun Shi ,&nbsp;Jie Zhao ,&nbsp;Cheng-Niu Wang ,&nbsp;Wei-Jia Chen ,&nbsp;Bao-Lun Zhu ,&nbsp;Jun-Jie Qian ,&nbsp;Wei Guan ,&nbsp;Bo Jiang","doi":"10.1016/j.neuropharm.2024.110198","DOIUrl":"10.1016/j.neuropharm.2024.110198","url":null,"abstract":"<div><div>Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis during chronic stress is essential for depression neurobiology. As the latest member of the RFamide peptide family in mammals, pyroglutamylated RFamide peptide (QRFP) is closely implicated in neuroendocrine maintenance by activating G-protein-coupled receptor 103 (GPR103). We hypothesized that QRFP and GPR103 might contribute to chronic stress-induced depression by promoting corticotropin-releasing hormone (CRH) release from neurons in the paraventricular nucleus (PVN), and various methods were employed in this study, with male C57BL/6J mice adopted as the experimental subjects. Chronic stress induced not only depression-like behaviors but also significant enhancement in QRFP and GPR103 in the PVN. Genetic overexpression of QRFP/GPR103 and stereotactic infusion of QRFP-26/QRFP-43 peptide in the PVN all mimicked chronic stress that induced various depression-like phenotypes in naïve mice, and this was mediated by promoting CRH biosynthesis and HPA activity. In contrast, genetic knockdown of QRFP/GPR103 in the PVN produced notable antidepressant-like effects in mice exposed to chronic stress. Furthermore, genetic knockout of QRFP also protected against chronic stress in mice. In addition, both the C-terminal biological region of QRFP and the downstream PKA/PKC-CREB signaling coupled to GPR103 stimulation underlie the role of QRFP and GPR103 in depression. Collectively, QRFP and GPR103 in PVN neurons could be viable targets for novel antidepressants.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"262 ","pages":"Article 110198"},"PeriodicalIF":4.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prelimbic cortex perineuronal net expression and social behavior: Impact of adolescent intermittent ethanol exposure","authors":"Trevor T. Towner,&nbsp;Harper J. Coleman,&nbsp;Matthew A. Goyden,&nbsp;Andrew S. Vore,&nbsp;Kimberly M. Papastrat,&nbsp;Elena I. Varlinskaya,&nbsp;David F. Werner","doi":"10.1016/j.neuropharm.2024.110195","DOIUrl":"10.1016/j.neuropharm.2024.110195","url":null,"abstract":"<div><div>Adolescent intermittent ethanol (AIE) exposure in rats leads to social deficits. Parvalbumin (PV) expressing fast-spiking interneurons in the prelimbic cortex (PrL) contribute to social behavior, and perineuronal nets (PNNs) within the PrL preferentially encompass and regulate PV interneurons. AIE exposure increases PNNs, but it is unknown if this upregulation contributes to AIE-induced social impairments. The current study was designed to determine the effect of AIE exposure on PNN expression in the PrL and to assess whether PNN dysregulation contributes to social deficits elicited by AIE. cFos-LacZ male and female rats were exposed every other day to tap water or ethanol (4 g/kg, 25% w/v) via intragastric gavage between postnatal day (P) 25–45. We evaluated neuronal activation by β-galactosidase expression and PNN levels either at the end of the exposure regimen on P45 and/or in adulthood on P70. In addition, we used Chondroitinase ABC (ChABC) to deplete PNNs following adolescent exposure (P48) and allowed for PNN restoration before social testing in adulthhod. AIE exposure increased PNN expression in the PrL of adult males, but decreased PNNs immediately following AIE. Vesicular glutamate transporter 2 (vGlut2) and vesicular GABA transporter (vGat) near PNNs were downregulated only in AIE-exposed females. Gene expression of PNN components was largely unaffected by AIE exposure. Removal and reestablishment of PrL PNNs by ChABC led to upregulation of PNNs and social impairments in males, regardless of adolescent exposure. These data suggest that AIE exposure in males upregulates PrL PNNs that likely contribute to social impairments induced by AIE.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"262 ","pages":"Article 110195"},"PeriodicalIF":4.6,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of matrix metalloproteinases to reduce blood brain barrier disruption and haemorrhagic transformation in ischaemic stroke: Go broad or go narrow?","authors":"Hala Kawa ,&nbsp;Zubair Ahmed ,&nbsp;Arshad Majid ,&nbsp;Ruoli Chen","doi":"10.1016/j.neuropharm.2024.110192","DOIUrl":"10.1016/j.neuropharm.2024.110192","url":null,"abstract":"<div><div>Ischaemic stroke characterises impulsive cerebral-region hypoxia due to deep intracerebral arteriole blockage, often accompanied by permanent cerebral infarction and cognitive impairment. Thrombolysis with recombinant tissue plasminogen activator (rtPA) and thrombectomy remain the only guidance-approved therapies. However, emerging data draws clear links between such therapies and haemorrhage transformation, which occur when cerebral vasculature is damaged during ischaemia/reperfusion. Studies have shown that matrix metalloproteinases (MMPs) play a significant role in haemorrhage transformation, by depleting the extracellular matrix (ECM) and disrupting the blood brain barrier (BBB). Inhibitors of MMPs may be used to prevent ischaemic stroke patients from BBB disruption and haemorrhage transformation, particularly for those receiving rtPA treatment. Preclinical studies found that inhibition of MMPs with agents or in knock out mice, effectively reduced BBB disruption and infarct volume, leading to improved ischaemic stroke outcomes. At present, MMP inhibition is not an approved therapy for stroke patients. There remain concerns about timing, dosing, duration of MMP inhibition and selection of either broad spectrum or specific MMP inhibitors for stroke patients. This review aims to summarize current knowledge on MMP inhibition in ischaemic stroke and explore whether a broad spectrum or a specific MMP inhibitor should be used for ischaemic stroke patient treatment. It is crucial to inhibit MMP activities early and sufficiently to ensure BBB intact during ischaemia and reperfusion, but also to reduce side effects of MMP inhibitors to minimum. Recent advance in stroke therapy by thrombectomy could aid in such treatment with intra-arterially delivery of MMP inhibitors (and/or antioxidants).</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"262 ","pages":"Article 110192"},"PeriodicalIF":4.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A bibliometric analysis of research on empathy for pain","authors":"Teng He ,&nbsp;Siqi Yang ,&nbsp;Changmao Zhu ,&nbsp;Bingyuan Zhang ,&nbsp;Qi Zhang ,&nbsp;Yawei Ji ,&nbsp;Yuanyuan Wang ,&nbsp;Riyue Jiang","doi":"10.1016/j.neuropharm.2024.110193","DOIUrl":"10.1016/j.neuropharm.2024.110193","url":null,"abstract":"<div><div>Empathy for pain encompasses the processes of perceiving, understanding, and responding to the pain of others, playing a crucial role in social interaction and individual development. The increasing interest in this field has led to a surge in related publications; however, the overall quantity and quality of these works remain uncertain. To address this issue, we conducted a bibliometric analysis of research on empathy for pain. Our study meticulously examined 479 publications to provide a comprehensive analysis of bibliographic elements such as annual publication trends, authorship, country of origin, institutional affiliations, journals, and keywords. Our findings indicate that, although there has been a rise in research on empathy for pain in recent years, the volume remains insufficient and is predominantly concentrated in a few countries, authors, and institutions. Additionally, current research mainly focuses on four primary areas: perception, pain, empathy, and emotion. We assert that future research will likely explore the relationship between EEG measurements and empathy for pain to determine if such measurements can effectively quantify empathy, thereby enhancing clinical management.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"262 ","pages":"Article 110193"},"PeriodicalIF":4.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prefrontal TNRC6A mediates anxiety-like behaviour by regulating CRF through the maintenance of miR-21-3p stability","authors":"Gui-Feng Lu ,&nbsp;Xin Yang ,&nbsp;Zhi Xiao ,&nbsp;Jia-Zhan Huang ,&nbsp;Yi-Han Jiang ,&nbsp;Meng-Qi Huang ,&nbsp;Fei Geng","doi":"10.1016/j.neuropharm.2024.110194","DOIUrl":"10.1016/j.neuropharm.2024.110194","url":null,"abstract":"<div><div>Anxiety is an emotional response to a potential threat. It is characterized by worry, feelings of tension, and physical changes. Trinucleotide repeat containing adaptor 6A (TNRC6A) binds to argonaute (AGO) proteins and microRNAs to form the miRNA-induced silencing complex (miRISC), which mediates mRNA degradation, storage, and translational repression functions. However, whether TNRC6A is involved in anxiety regulation remains unknown.</div><div>In this study, TNRC6A was downregulated in the prefrontal cortex (PFC) of mice exposed to acute restraint stress. Inhibition of TNRC6A in PFC induced anxious behaviour. RNA immunoprecipitation, RNA pull-down and real-time quantitative PCR revealed that TNRC6A directly binds to miR-21-3p and maintains its stability. Intriguingly, miR-21-3p was downregulated in the PFC of acute stress mice, whereas overexpression of miR-21-3p significantly reduced anxiety-like behaviour. Furthermore, miR-21-3p knockdown significantly increased the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) in the PFC pyramidal neurons. Dual luciferase assay and western blotting confirmed that miR-21-3p binds to the 3 ‘UTR region of corticotropin-releasing factor (CRF) mRNA and regulates CRF and cAMP-response element binding protein (CREB) expression. These results confirm that low levels of TNRC6A in the PFC decrease the stability of miR-21-3p which promotes the up-regulation of CRF, leading to the development of anxiety-like behaviours. This research provides insight into a novel molecular mechanism by which TNRC6A regulates anxiety behaviour through the miR-21-3p/CRF signalling axis.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"262 ","pages":"Article 110194"},"PeriodicalIF":4.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glyphosate impairs both structure and function of GABAergic synapses in hippocampal neurons","authors":"Giuseppe Chiantia ,&nbsp;Debora Comai ,&nbsp;Enis Hidisoglu ,&nbsp;Antonia Gurgone ,&nbsp;Claudio Franchino ,&nbsp;Valentina Carabelli ,&nbsp;Andrea Marcantoni ,&nbsp;Maurizio Giustetto","doi":"10.1016/j.neuropharm.2024.110183","DOIUrl":"10.1016/j.neuropharm.2024.110183","url":null,"abstract":"<div><div>Glyphosate (Gly) is a broad-spectrum herbicide responsible for the inhibition of the enzyme 5-enolpyruvylshikimate-3-phosphate synthase known to be expressed exclusively in plants and not in animals. For decades Gly has been thought to be ineffective in mammals, including humans, until it was demonstrated that rodents treated with the Gly-based herbicide Roundup showed reduced content of neurotransmitters (e.g., serotonin, dopamine, norepinephrine, and acetylcholine), increased oxidative stress in the brain associated with anxiety and depression-like behaviors and learning and memory deficits. Despite compelling evidence pointing to a neurotoxic effect of Gly, an in-depth functional description of its effects on synaptic transmission is still lacking. To investigate the synaptic alterations dependent on Gly administration we performed whole-cell patch-clamp recordings and immunocytochemistry on mouse primary cultured hippocampal neurons. Our findings reveal that 30 min incubation of Gly at the acceptable daily intake dose severely impaired inhibitory GABAergic synapses. Further analysis pointed out that Gly decreased the number of postsynaptic GABA_A receptors and reduced the amplitude of evoked inhibitory postsynaptic currents, the readily releasable pool size available for synchronous release and the quantal size. Finally, a decreased number of release sites has been observed. Consistently, morphological analyses showed that the density of both pre- and post-synaptic inhibitory compartments decorating pyramidal cell dendrites was reduced by Gly. In conclusion, our experiments define for the first time the effects induced by Gly on GABAergic synapses, and reveal that Gly significantly impairs both pre- and postsynaptic mechanisms.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"262 ","pages":"Article 110183"},"PeriodicalIF":4.6,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinically-probed mechanisms of action in Fragile-X syndrome fail to normalize translational EEG phenotypes in Fmr1 knockout mice","authors":"Philipp Janz ,&nbsp;Marie Bainier ,&nbsp;Samuel Marashli,&nbsp;Simon Gross,&nbsp;Roger L. Redondo","doi":"10.1016/j.neuropharm.2024.110182","DOIUrl":"10.1016/j.neuropharm.2024.110182","url":null,"abstract":"<div><div>Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by Fragile X Messenger Ribonucleoprotein (FMRP) deficiency. Electroencephalogram (EEG) changes in FXS include alterations of oscillatory activity and responses to sensory stimuli, some of which have been back-translated into rodent models by knocking-out the Fragile X messenger ribonucleoprotein 1 gene (Fmr1-KO). However, the validity of these EEG phenotypes as objective biomarkers requires further investigation.</div><div>Potential pharmacotherapies such as mGluR5 inhibitors (e.g. CTEP; 2-chloro-4-((2,5-dimethyl-1-(4-(trifluoromethoxy)phenyl)-1H-imidazole-4-yl)ethynyl)pyridine), GABA_BR agonists (e.g. arbaclofen) and δ-containing GABA_AR agonists (e.g. gaboxadol) have not translated into clinical success despite rescuing many phenotypes in the Fmr1-KO model. Yet none of these treatments have been assessed on EEG phenotypes in the Fmr1-KO model. Therefore, we set out to discover new EEG phenotypes in Fmr1-KO mice, using “task-free” and auditory-evoked (AEPs) and visually-evoked potential (VEP) paradigms, and probe their modulation by CTEP, arbaclofen and gaboxadol, using within-subjects designs.</div><div>First, we report Fmr1-KO-associated EEG abnormalities that closely resemble those observed in FXS, including elevated gamma-band power, reduced alpha/beta-band coherence, increased AEPs and delayed VEPs. Secondly, we found that pharmacological treatment, at best, only partially normalized EEG phenotypes. CTEP restored alpha/beta-band coherence and AEP amplitudes but failed to normalize gamma power and VEP latencies. Conversely, arbaclofen reduced gamma power but did not restore coherence or AEP amplitudes and further delayed VEPs. Gaboxadol did not normalize any EEG phenotypes.</div><div>We conclude that these compounds have limited ability to normalize these EEG phenotypes.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"262 ","pages":"Article 110182"},"PeriodicalIF":4.6,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranasal AdipoRon mitigates motor and cognitive deficits in hemiparkinsonian rats through neuroprotective mechanisms against oxidative stress and synaptic dysfunction","authors":"Soraya Alimohammadi ,&nbsp;Gisou Mohaddes ,&nbsp;Rana Keyhanmanesh ,&nbsp;Seyed Zanyar Athari ,&nbsp;Negin Azizifar ,&nbsp;Fereshteh Farajdokht","doi":"10.1016/j.neuropharm.2024.110180","DOIUrl":"10.1016/j.neuropharm.2024.110180","url":null,"abstract":"<div><div>While motor symptoms are the most well-known manifestation of Parkinson's disease (PD), patients may also suffer from non-motor signs like cognitive impairments. The adiponectin receptor agonist AdipoRon (Adipo) has shown neuroprotective effects in preclinical studies. The objective of this study was to determine the potential benefits of chronic intranasal treatment of Adipo on motor function and cognitive performance in a hemiparkinsonian rat model caused by injecting 6-hydroxydopamine (6-OHDA) into the left forebrain bundle. After one week, PD rats were given either a vehicle or one of three dosages of Adipo (0.1, 1, and 10 μg) or levodopa (10 mg/kg orally) daily for 21 days. Recognition and spatial memory were determined using the novel object recognition test (NORT) and the Barnes maze test, respectively. The hippocampal tissues of the animals were harvested to examine oxidative stress status as well as the protein expressions of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD-95). In hemiparkinsonian rats, motor impairments, recognition memory, and spatial memory were all improved by chronic intranasal Adipo at 1 and 10 μg. Furthermore, we found that unilateral 6-OHDA injection elevated hippocampal oxidative stress (ROS) while concurrently reducing total antioxidant capacity (TAC), BDNF, PSD-95, and antioxidant enzymes (SOD, GPx). However, Adipo 10 μg significantly reduced these biochemical alterations in the hippocampus of 6-OHDA-lesioned rats. Chronic intranasal Adipo ameliorated spatial and recognition memory deterioration in hemiparkinsonian rats, presumably by increasing hippocampal synaptic protein levels, reducing oxidative stress, and increasing BDNF.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"262 ","pages":"Article 110180"},"PeriodicalIF":4.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of ventral pallidum-projecting neurons in the nucleus accumbens via 5-HT2C receptor stimulation regulates motivation for wheel running in male mice","authors":"Kazuhei Niitani,&nbsp;Ryoma Nishida,&nbsp;Yusaku Futami,&nbsp;Naoya Nishitani,&nbsp;Satoshi Deyama,&nbsp;Katsuyuki Kaneda","doi":"10.1016/j.neuropharm.2024.110181","DOIUrl":"10.1016/j.neuropharm.2024.110181","url":null,"abstract":"<div><div>Rodents have a strong motivation for wheel running; however, the neural mechanisms that regulate their motivation remain unknown. We investigated the possible involvement of serotonin (5-HT) systems in regulating motivation for wheel running in male mice. Systemic administration of a 5-HT_1A receptor antagonist (WAY100635) increased the number of wheel rotations, whereas administration of a 5-HT_2A or 5-HT_2C receptor antagonist (volinanserin or SB242084, respectively) decreased it. In the open field test, neither WAY100635 nor volinanserin affected locomotor activity, whereas SB242084 increased locomotor activity. To identify the brain regions on which these antagonists act, we locally injected these into the motivational circuitry, including the nucleus accumbens (NAc), dorsomedial striatum (DM-Str), and medial prefrontal cortex (mPFC). Injection of SB242084 into the NAc, but not the DM-Str or mPFC, reduced the number of wheel rotations without altering locomotor activity. The local administration of WAY100635 or volinanserin to these brain regions did not affect the number of wheel rotations. Immunohistochemical analyses revealed that wheel running increased the number of c-Fos-positive cells in the NAc medial shell (NAc-MS), which was reduced by systemic SB242084 administration. <em>In vitro</em> slice whole-cell recordings showed that bath application of the 5-HT_2C receptor agonist lorcaserin increased the frequency of spontaneous excitatory and inhibitory postsynaptic currents in the ventral tegmental area (VTA)-projecting neurons, whereas it only increased the frequency of spontaneous excitatory postsynaptic currents in ventral pallidum (VP)-projecting neurons in the NAc-MS. These findings suggest that the activation of VP-projecting NAc-MS neurons via 5-HT_2C receptor stimulation regulates motivation for wheel running.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"261 ","pages":"Article 110181"},"PeriodicalIF":4.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}