Neuropharmacology最新文献_第2页

Activation of Epac2 improves Aβ-induced impairment of memory retrieval in an acute model of Alzheimer's disease 在阿尔茨海默病急性模型中，激活Epac2可改善a β诱导的记忆恢复损伤

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-04-14 DOI: 10.1016/j.neuropharm.2025.110468

Tong Zhang , Yuequ Zhang , Pascal Chameau , Tingting Chen , Alejandro Marmolejo-Garza , Wanda Douwenga , Amalia M. Dolga , Helmut W. Kessels , Martina Schmidt , Ulrich L.M. Eisel

{"title":"Activation of Epac2 improves Aβ-induced impairment of memory retrieval in an acute model of Alzheimer's disease","authors":"Tong Zhang , Yuequ Zhang , Pascal Chameau , Tingting Chen , Alejandro Marmolejo-Garza , Wanda Douwenga , Amalia M. Dolga , Helmut W. Kessels , Martina Schmidt , Ulrich L.M. Eisel","doi":"10.1016/j.neuropharm.2025.110468","DOIUrl":"10.1016/j.neuropharm.2025.110468","url":null,"abstract":"<div><div>Impaired memory retrieval is one of the cognitive markers in the early stage of Alzheimer's Disease (AD). Previous studies report that exchange protein directly activated by cAMP 2 (Epac2) plays a specific and time-limited role in promoting memory retrieval. In this study, we investigated the effect of a novel Epac2 activator, S220, on neuronal and synaptic activities, and memory impairment in an acute AD mouse model. S220 treatment increased the firing rate of action potential and intracellular calcium in primary neuronal cultures. Moreover, S220 treatment increased synaptic currents in CA1 neurons. In the acute AD mouse model, intrahippocampal injection of amyloid-β (Aβ) oligomers impaired memory performance. Notably, administering S220 20 min before retention of contextual fear conditioning recovered the Aβ-induced memory impairment, suggesting an enhancing effect on memory retrieval. Collectively, our data demonstrate that the novel Epac2 activator S220 promotes synaptic communication and neuronal firing, and thereby improves Aβ-induced memory impairment via enhancing memory retrieval, indicating the role of Epac2 as a potential treatment target for AD.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"274 ","pages":"Article 110468"},"PeriodicalIF":4.6,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835056","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}

引用次数: 0

Aged mice exhibit faster acquisition of intravenous opioid self-administration with variable effects on intake 老年小鼠表现出更快获得静脉注射阿片类药物的自我管理，对摄入量有不同的影响

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-04-12 DOI: 10.1016/j.neuropharm.2025.110464

Amanda L. Sharpe , Laci R. Liter , Darius Donohue , Kelsey A. Carter , Patricia Vangeneugden , Sofia M. Weaver , Michael B. Stout , Michael J. Beckstead

{"title":"Aged mice exhibit faster acquisition of intravenous opioid self-administration with variable effects on intake","authors":"Amanda L. Sharpe , Laci R. Liter , Darius Donohue , Kelsey A. Carter , Patricia Vangeneugden , Sofia M. Weaver , Michael B. Stout , Michael J. Beckstead","doi":"10.1016/j.neuropharm.2025.110464","DOIUrl":"10.1016/j.neuropharm.2025.110464","url":null,"abstract":"<div><div>Although opioid abuse is more prevalent in young individuals, the rates of opioid use, overdose, and use disorders continue to climb among the elderly. Little is known about the biology underlying abuse potential in a healthy, aged population, in part due to technical and logistical difficulties testing intravenous self-administration in aged rodents. The goal of this study was to address a critical gap in the literature regarding age-dependent effects in opioid (remifentanil and fentanyl) self-administration. Male and female C57Bl/6J and C57Bl/6NJ mice were divided into young (mean: 19 weeks) and old (mean: 101 weeks) groups and were trained to self-administer intravenous fentanyl or remifentanil in daily operant sessions. Acquisition, intake, and cue-responding after forced abstinence were measured for both drugs, and a dose-response curve and dose-escalation were conducted for remifentanil and fentanyl, respectively. Surprisingly, old mice learned to self-administer both remifentanil and fentanyl faster and more accurately than young mice. Baseline intake of remifentanil was also greater in old mice compared to the young group; however, we did not see increased intake of fentanyl with age at either dose tested. Furthermore, old mice showed greater responding for cues previously associated with remifentanil after a forced abstinence, but this result was not observed with fentanyl. This first report of opioid self-administration in greater than 20-month-old mice suggests that old mice have an increased vulnerability for opioid use compared to younger counterparts, underscoring the importance of future work to uncover the biological mechanisms that are responsible.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"274 ","pages":"Article 110464"},"PeriodicalIF":4.6,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835055","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}

引用次数: 0

The role of testosterone in modulating positive and negative empathy in social interactions 睾酮在调节社会交往中积极和消极共情中的作用

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-04-12 DOI: 10.1016/j.neuropharm.2025.110465

Shiwei Zhuo , Yinhua Zhang , Chennan Lin , Wen Wu , Weiwei Peng

{"title":"The role of testosterone in modulating positive and negative empathy in social interactions","authors":"Shiwei Zhuo , Yinhua Zhang , Chennan Lin , Wen Wu , Weiwei Peng","doi":"10.1016/j.neuropharm.2025.110465","DOIUrl":"10.1016/j.neuropharm.2025.110465","url":null,"abstract":"<div><div>Empathy encompasses both negative (e.g., distress) and positive (e.g., shared joy) dimensions, yet the effects of testosterone on positive empathy and its modulation of intrinsic neural dynamics remain underexplored. This double-blind, placebo-controlled study examined how testosterone influences neural sensitivity to empathy within social inclusion and exclusion contexts, as well as its impact on resting-state EEG microstates—millisecond-scale transient patterns of brain activity. Healthy male participants received either testosterone or placebo before completing resting-state EEG recordings and an empathy task featuring social scenarios. While self-reported empathy ratings remained unchanged, testosterone amplified neurophysiological responses: it enhanced anterior N2 amplitude (250–310 ms), associated with negative empathy toward social exclusion, and increased posterior α-event-related desynchronization (8.28–10 Hz; 1226–1901 ms), linked to positive empathy during social inclusion. These findings suggest that testosterone enhances neural responsiveness to both threatening and affiliative social cues, reinforcing its role in adaptive social vigilance. Resting-state EEG microstate analysis further revealed that testosterone prolonged the temporal dominance of microstate E—a centro-parietal activity pattern associated with interoceptive awareness and emotional processing. Notably, these microstate E changes predicted increased emotional empathy across both positive and negative contexts. Together, our findings suggest that testosterone indirectly enhances empathy-related responsiveness by amplifying baseline interoceptive sensitivity to socially salient stimuli. These dual effects—enhanced intrinsic interoceptive processing and heightened neural reactivity to social cues—position testosterone as a key neuromodulator of context-adaptive social perception.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"274 ","pages":"Article 110465"},"PeriodicalIF":4.6,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842671","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}

引用次数: 0

Kinsenoside attenuates ER stress and inhibits inflammatory responses through IL-10/STAT/SOCS3 pathway in chronic pain relief 人参皂苷通过IL-10/STAT/SOCS3通路减轻内质网应激，抑制炎症反应，缓解慢性疼痛

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-04-11 DOI: 10.1016/j.neuropharm.2025.110463

Wei Wang , Yingzhuo Ding , Chunxia Yu , Qingqing Chi , Xia Fu , Mengjiao Deng , Dongxia Duan , Jinbao Wei , Ronghua Ding , Yufei Xi , Qin Li , Le Ma

{"title":"Kinsenoside attenuates ER stress and inhibits inflammatory responses through IL-10/STAT/SOCS3 pathway in chronic pain relief","authors":"Wei Wang , Yingzhuo Ding , Chunxia Yu , Qingqing Chi , Xia Fu , Mengjiao Deng , Dongxia Duan , Jinbao Wei , Ronghua Ding , Yufei Xi , Qin Li , Le Ma","doi":"10.1016/j.neuropharm.2025.110463","DOIUrl":"10.1016/j.neuropharm.2025.110463","url":null,"abstract":"<div><div>Neuro-inflammation contributes to neuropathic pain by sensitizing ionic channels. Kinsenoside, a traditional Chinese medicine, has recognized anti-inflammatory properties. However, it remains unclear whether kinsenoside can be used for pain therapy. Network pharmacology analysis revealed that 57 % of its targets are associated with pain, including inflammation and synaptic transmission. The analgesic effects of kinsenoside were confirmed in SNL and formalin rat models, with ED50 values of 47.99 μg and 36.80 μg, respectively. Transcriptome and WGCNA analyses indicated the involvement of cytokine release, anti-inflammatory activity, and synapse enrichment in the blue module. Furthermore, we confirmed that kinsenoside's efficacy was mainly mediated by IL-10 induction, phosphorylation of STAT3, and SOCS3 expression. Pretreatment with kinsenoside significantly inhibited the release of TNF-α, IL-1β, and IL-6. Kinsenoside also attenuated ER stress in both microglia and neural cells. Molecular docking analysis demonstrated significantly high binding energies of IL-10, STAT3, and SOCS3 with MHC. Additionally, whole-cell recordings revealed that bath application of kinsenoside reduced the frequency and amplitude of spinal glutamatergic transmission in a dose-dependent manner. In summary, pharmacological prediction and biological validation collectively indicate that kinsenoside significantly exerts significant analgesic effects by attenuating ER stress and inhibiting inflammatory responses via the IL-10/p-STAT3/SOCS3 axis, precisely regulating spinal glutamatergic transmission for pain relief.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"273 ","pages":"Article 110463"},"PeriodicalIF":4.6,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829630","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}

引用次数: 0

Demethylase FTO in the cerebrospinal fluid-contacting nucleus of mice contributes to neuropathic pain via mediating m6A demethylation of P2rx4 mRNA 小鼠脑脊液接触核中的去甲基化酶FTO通过介导P2rx4 mRNA的m6A去甲基化参与神经性疼痛

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-04-11 DOI: 10.1016/j.neuropharm.2025.110462

Yu-Ting Zhang, Wei-Long Huang, Yi-Jun Zhang, Li-Cai Zhang

{"title":"Demethylase FTO in the cerebrospinal fluid-contacting nucleus of mice contributes to neuropathic pain via mediating m6A demethylation of P2rx4 mRNA","authors":"Yu-Ting Zhang, Wei-Long Huang, Yi-Jun Zhang, Li-Cai Zhang","doi":"10.1016/j.neuropharm.2025.110462","DOIUrl":"10.1016/j.neuropharm.2025.110462","url":null,"abstract":"<div><div>N6-methyladenosine (m6A) modification plays a crucial role in pain regulation by modulating pain-related gene expression. The cerebrospinal fluid-contacting nucleus (CSF-contacting nucleus) is closely associated with pain, and downregulation of P2X4 receptor (P2X4R) expression in this region alleviates hyperalgesia. However, the relationship between m6A modification and P2X4R in CSF-contacting nucleus remains unclear. This study aims to investigate the role and potential mechanisms of the m6A demethylase fat mass and obesity-associated protein (FTO) and P2X4R in neuropathic pain (NP) induced by spared nerve injury (SNI) in male mice. We observed decreased m6A levels and upregulated FTO expression in the CSF-contacting nucleus of SNI mice. FTO was primarily expressed in neurons of the CSF-contacting nucleus, with symmetrical distribution across its bilateral regions. In CSF-contacting nucleus, FTO overexpression reduced m6A methylation and promoted pain, while FTO inhibition increased m6A levels and alleviated pain hypersensitivity. The administration of the FTO inhibitor meclofenamic acid (MA) into CSF-contacting nucleus alleviated pain. FTO regulated the expression of <em>P2rx4</em> mRNA and protein in CSF-contacting nucleus. Furthermore, <em>P2rx4</em> mRNA is a downstream target of FTO-mediated m6A demethylation. In summary, the m6A demethylase FTO contributes to NP by upregulating the expression of <em>P2rx4</em> mRNA and protein through mediating m6A demethylation of <em>P2rx4</em> mRNA. Therefore, the m6A demethylase FTO in CSF-contacting nucleus may represent a novel therapeutic target for NP.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"273 ","pages":"Article 110462"},"PeriodicalIF":4.6,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829628","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}

引用次数: 0

Trace amine-associated receptor 1 agonists reduce alcohol drinking and differentially modulate dopamine release in the nucleus accumbens of alcohol preferring mice 微量胺相关受体1激动剂减少酒精偏好小鼠伏隔核的饮酒和差异调节多巴胺释放

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-04-10 DOI: 10.1016/j.neuropharm.2025.110460

Charles Houdant , Mandy Lamarche , Grégory Fouquet , Véronique Debuysscher , Jolanta Orzelska-Górka , Marta Kruk-Slomka , Grażyna Biała , Jérôme Jeanblanc , Mickaël Naassila

{"title":"Trace amine-associated receptor 1 agonists reduce alcohol drinking and differentially modulate dopamine release in the nucleus accumbens of alcohol preferring mice","authors":"Charles Houdant , Mandy Lamarche , Grégory Fouquet , Véronique Debuysscher , Jolanta Orzelska-Górka , Marta Kruk-Slomka , Grażyna Biała , Jérôme Jeanblanc , Mickaël Naassila","doi":"10.1016/j.neuropharm.2025.110460","DOIUrl":"10.1016/j.neuropharm.2025.110460","url":null,"abstract":"<div><div>Current treatments for alcohol use disorder have limited efficacy underscoring the need for novel therapeutic targets. Trace amine-associated receptor 1 (TAAR1) is a promising candidate due to its ability to act as a brake on dopaminergic transmission and alcohol consumption. However, both the relative efficacy of full and partial TAAR1 agonists in reducing alcohol-related behaviors and their underlying mechanisms of action remain unclear. In this study, we evaluated the effects of the full agonist RO5166017 and the partial agonist RO5263397 on alcohol consumption using an intermittent access protocol in alcohol-preferring male C57BL/6JRj mice. Given their distinct pharmacological and electrophysiological properties, we also investigated the effects of these agonists on presynaptic dopaminergic transmission using fast-scan cyclic voltammetry in the nucleus accumbens, a key structure involved in alcohol reinforcement. Full and partial TAAR1 agonists reduced alcohol intake by 25 % and 43 %, respectively. We further report that these agonists exhibit opposite effects on dopamine release under basal conditions, but that these effects are reversed in animals chronically exposed to alcohol<em>.</em> The reversal in dopamine release did not result from alcohol-induced modifications of TAAR1 or D2 receptor expression. Our findings highlight the therapeutic potential of TAAR1 agonists for alcohol addiction and reveal important functional differences between full and partial agonists. Further research is needed to determine the clinical relevance of these distinct pharmacodynamic profiles and optimize TAAR1-targeting pharmacotherapies.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"274 ","pages":"Article 110460"},"PeriodicalIF":4.6,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838380","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}

引用次数: 0

Sex-dependent role of the dorsolateral septum in shaping contextual cocaine memory strength 背外侧隔在形成情境可卡因记忆强度中的性别依赖作用

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-04-07 DOI: 10.1016/j.neuropharm.2025.110459

S. Qi , J.L. Ritchie , D.A. Soto , A.Y. Pruitt , D.A. Reeves , L.M. Artimenia , R.A. Fuchs

{"title":"Sex-dependent role of the dorsolateral septum in shaping contextual cocaine memory strength","authors":"S. Qi , J.L. Ritchie , D.A. Soto , A.Y. Pruitt , D.A. Reeves , L.M. Artimenia , R.A. Fuchs","doi":"10.1016/j.neuropharm.2025.110459","DOIUrl":"10.1016/j.neuropharm.2025.110459","url":null,"abstract":"<div><div>Established memories can be destabilized, updated, and reconsolidated into long-term memory stores. Memory updating and reconsolidation can alter the strength of maladaptive contextual drug memories and consequently context-induced drug craving and relapse. The dorsolateral septum (dlS) is a GABAergic nucleus that receives dense direct input from the cornu ammonis 3 regions of the dorsal hippocampus, a brain region that is critical for the maintenance of contextual cocaine memories. Accordingly, we tested the hypothesis that neuronal activity in the dlS regulates the strength of cocaine-predictive contextual memories prior to reconsolidation. Male and female Sprague-Dawley rats received cocaine self-administration training followed by extinction training in two different environmental contexts. After the last extinction training session, the rats were placed back into the cocaine-predictive context to retrieve and destabilize their cocaine-related contextual memories. Immediately or 6 h after memory retrieval, the rats received intra-dlS vehicle or baclofen/muscimol (B/M; GABA<sub>B/A</sub> agonists) infusions to inhibit neuronal activity during or after memory updating/reconsolidation, respectively. Resulting changes in cocaine and extinction memory strength were assessed based on the magnitude of unreinforced lever responding in the two contexts. Intra-dlS B/M infusion immediately after memory retrieval increased subsequent context-induced cocaine seeking behaviors in male rats, but not in female rats, whereas delayed B/M treatment had no effects in male rats. Together these findings suggest that the dlS is selectively engaged during memory updating/reconsolidation to reduce the strength of cocaine memories in males, possibly contributing to sex differences in the progression of cocaine use disorder.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"273 ","pages":"Article 110459"},"PeriodicalIF":4.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143808159","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}

引用次数: 0

Kappa opioid receptors diminish spontaneous dopamine signals in awake mice through multiple mechanisms Kappa阿片受体通过多种机制减少清醒小鼠的自发多巴胺信号

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-04-07 DOI: 10.1016/j.neuropharm.2025.110458

Conner W. Wallace , Katherine M. Holleran , Clare Y. Slinkard , Samuel W. Centanni , Christopher C. Lapish , Sara R. Jones

{"title":"Kappa opioid receptors diminish spontaneous dopamine signals in awake mice through multiple mechanisms","authors":"Conner W. Wallace , Katherine M. Holleran , Clare Y. Slinkard , Samuel W. Centanni , Christopher C. Lapish , Sara R. Jones","doi":"10.1016/j.neuropharm.2025.110458","DOIUrl":"10.1016/j.neuropharm.2025.110458","url":null,"abstract":"<div><div>The role of the dynorphin/kappa opioid receptor (KOR) system in dopamine (DA) regulation has been extensively investigated. KOR activation reduces extracellular DA concentrations, but the exact mechanism(s) through which this is accomplished are not fully elucidated. To explore KOR influences on real-time DA fluctuations, we used the photosensor dLight1.2 with fiber photometry in the nucleus accumbens (NAc) core of freely moving male and female C57BL/6J mice. First, we established that the rise and fall of spontaneously arising DA signals were due to DA release and reuptake, respectively. Next, mice were systemically administered the KOR agonist U50,488H in the presence or absence of the KOR antagonist aticaprant. U50,488H reduced both the amplitude and width of spontaneous signals in both sexes. Further, the slope of the correlation between amplitude and width was increased, indicating that DA uptake rates were increased. U50,488H also reduced the frequency of occurrence of signals in males and females. The effects of KOR activation were stronger in males, while effects of KOR antagonism were stronger in females. Overall, KORs exerted significant inhibitory control over spontaneous DA signaling, acting through at least three mechanisms - inhibiting DA release, promoting DA transporter-mediated uptake, and reducing the frequency of signals.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"273 ","pages":"Article 110458"},"PeriodicalIF":4.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829627","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}

引用次数: 0

Does the lateral hypothalamus govern the transition between appetitive and consummatory feeding? 外侧下丘脑是否控制食欲进食和圆满进食之间的过渡？

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-04-05 DOI: 10.1016/j.neuropharm.2025.110438

Mette Kongstorp , Mahesh M. Karnani , James E. McCutcheon

引用次数: 0

Calcitonin gene-related peptide (CGRP) exerts membrane, cellular and synaptic actions on serotonergic dorsal raphe neurons ex vivo: Functional implications for a role in dorsal raphe-controlled functions 降钙素基因相关肽（CGRP）在体外对血清素能背缝神经元施加膜、细胞和突触作用：在背缝控制功能中的功能意义。

IF 4.6 2区医学

Neuropharmacology Pub Date : 2025-04-04 DOI: 10.1016/j.neuropharm.2025.110457

Yan Tong Yang , Cesar R. Romero-Leguizamón , Majid Sheykhzade , Yan Zhu , Kristi Anne Kohlmeier

{"title":"Calcitonin gene-related peptide (CGRP) exerts membrane, cellular and synaptic actions on serotonergic dorsal raphe neurons ex vivo: Functional implications for a role in dorsal raphe-controlled functions","authors":"Yan Tong Yang , Cesar R. Romero-Leguizamón , Majid Sheykhzade , Yan Zhu , Kristi Anne Kohlmeier","doi":"10.1016/j.neuropharm.2025.110457","DOIUrl":"10.1016/j.neuropharm.2025.110457","url":null,"abstract":"<div><div>Serotonin (5-HT) plays a role in limbic-controlled behaviors and is implicated in migraine, which is often co-morbid with cognitive-based affective disorders. The neuropeptide calcitonin gene-related peptide (CGRP) regulates vascular tone. Serotonin-acting drugs and CGRP receptor antagonists have proved therapeutic in management of migraine. Clinical interactions between the two systems have been shown, however, whether CGRP exerts direct actions on serotonergic Dorsal Raphe (DR) neurons is unknown. To fully understand the role of CGRP in control of behavior and to predict how CGRP targeted therapies (i.e. CGRP receptor antagonists) could alter DR neuronal activity, investigation of whether CGRP can directly affect 5-HT DR activity was conducted. Patch clamp electrophysiology and single photon calcium imaging in DR brain slices revealed that CGRP (10<sup>−6</sup> M) elicited postsynaptically mediated, potassium-involved outward currents in the majority of 5-HT DR cells. Miniature excitatory synaptic events were reduced in frequency. Further, intracellular calcium was reduced in the majority of neurons, which did not involve actions on the L-type calcium channel. The CGRP agonist SAX replicated effects on the membrane and intracellular calcium. In contrast, the CGRP receptor antagonist MK-3207 blocked the effects on outward current and attenuated the action of CGRP on reducing intracellular calcium. Despite inhibitory membrane and synaptic effects, no change was noted in firing rate. Our findings raise the intriguing possibility that the CGRP system plays a role in mediating limbic-controlled behaviors, at least in part, through direct actions on serotonergic DR neurons, however the effect of CGRP on DR 5-HT output remains to be investigated.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"273 ","pages":"Article 110457"},"PeriodicalIF":4.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795865","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}

引用次数: 0