Neuropharmacology最新文献

{"title":"Lactate: Beyond a mere fuel in the epileptic brain","authors":"Xiang Chen ,&nbsp;Xinjian Zhu","doi":"10.1016/j.neuropharm.2024.110273","DOIUrl":"10.1016/j.neuropharm.2024.110273","url":null,"abstract":"<div><div>Epilepsy, a prevalent neurological disorder characterized by spontaneous recurrent seizures, significantly impacts physiological and cognitive functions. Emerging evidence suggests a crucial role for metabolic factors, particularly lactate, in epilepsy. We discuss the applicability of the astrocyte-neuron lactate shuttle (ANLS) model during acute seizure events and examine lactate's metabolic adaptation in epilepsy progression. Additionally, the roles of lactate metabolism in microglia and oligodendrocytes are considered, aiming to supplement our understanding of neuro-glial metabolic interactions as extensions of the ANLS model. Additionally, lactate modulates neuronal excitability via its interaction with hydroxycarboxylic acid receptor 1 (HCAR1), alongside additional mechanisms involving acid-sensing ion channels (ASICs) and ATP-sensitive potassium (KATP) channels, which contribute as secondary modulatory pathways. In conclusion, we propose that lactate functions as more than a mere fuel source in the epileptic brain, offering potential insights into new therapeutic targets for seizure control.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"266 ","pages":"Article 110273"},"PeriodicalIF":4.6,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886045","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":"Hyperoside ameliorates neuropathic pain by modulating the astroglial reactivity in the vlPAG","authors":"Tianchi Gao ,&nbsp;Chenghao Wang ,&nbsp;Xiaotong Yang ,&nbsp;Zhiwei He ,&nbsp;Yanqing Wang ,&nbsp;Wenli Mi","doi":"10.1016/j.neuropharm.2024.110276","DOIUrl":"10.1016/j.neuropharm.2024.110276","url":null,"abstract":"<div><div>Hyperoside, a natural flavonoid, exhibits a wide range of biological activities, including analgesic effects on acute and chronic inflammatory pain. This study illustrates that repeated intraperitoneal administration or microinjection of hyperoside into the ventrolateral periaqueductal grey (vlPAG) alleviated mechanical allodynia, cold allodynia, and abnormal gait induced by spared nerve injury (SNI) in male mice. Furthermore, repeated hyperoside administration suppressed SNI-induced astrocyte reactivity in the vlPAG. Moreover, hyperoside alleviated the pain behaviors resulting from the pharmacogenetic activation of vlPAG astrocytes. These results suggest that hyperoside may effectively mitigate neuropathic pain and inhibit astroglial reactivity in the vlPAG, highlighting its potential as a viable therapeutic intervention for chronic neuropathic pain.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"266 ","pages":"Article 110276"},"PeriodicalIF":4.6,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882368","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":"Reversal of the motivational effects of tetrabenazine by NMDA receptor blockade","authors":"Artem Savchenko ,&nbsp;Salim Tarchokov ,&nbsp;Olga Dravolina ,&nbsp;Jana Lubec ,&nbsp;Gert Lubec ,&nbsp;Ilya Sukhanov","doi":"10.1016/j.neuropharm.2024.110277","DOIUrl":"10.1016/j.neuropharm.2024.110277","url":null,"abstract":"<div><h3>Background</h3><div>Apathy is a syndrome of decreased goal-directed activity, one of the main features of different brain disorders. Despite its high prevalence and life-threatening potential, there are currently very few options for its pharmacological treatment, which may be related to the lack of valid animal models.</div></div><div><h3>Aims</h3><div>The vesicular monoamine transporter 2 inhibitor tetrabenazine (TBZ) was used in this study to model apathy-related behavior in pathologies linked to a depletion of dopamine. The atypical dopamine transporter inhibitor CE-123 and the NMDA receptor antagonist MK-801 were evaluated for their effects on goal-directed activity in intact and TBZ-treated rats to compare dopamine and non-dopamine approaches.</div></div><div><h3>Methods</h3><div>To assess goal-directed behavior, the progressive ratio 3 (PR3) operant schedule of food reinforcement was conducted in adult male rats. To assess the motivational changes underlying the schedule, a model analysis based on the mathematical principles of reinforcement was applied.</div></div><div><h3>Results</h3><div>Treatment with TBZ (0.3 mg/kg) induced a decrease in response rate as the number of required responses increased. This effect was not accompanied by a decrease in the incentive value of the reinforcer or locomotor disturbances, suggesting that decreased tolerance to high effort demands was the underlying mechanism of the decrease in goal-directed activity. Treatment with MK-801 increased operant activity in both TBZ-treated and pharmacologically naïve rats.</div></div><div><h3>Conclusions</h3><div>Our results support the previously proposed view that the TBZ-treated rats can be a model of apathy-related behavior in pathologies linked to a depletion of dopamine and suggest that NMDA receptors are a potential therapeutic target for the development of novel approaches to the treatment of apathy in both dopamine-depleted and dopamine-intact states.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"266 ","pages":"Article 110277"},"PeriodicalIF":4.6,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877433","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":"Efficacy and safety of evenamide, a glutamate modulator, added to a second-generation antipsychotic in inadequately/poorly responding patients with chronic schizophrenia: Results from a randomized, double-blind, placebo-controlled, phase 3, international clinical trial","authors":"Ravi Anand ,&nbsp;Alessio Turolla ,&nbsp;Giovanni Chinellato ,&nbsp;Francesca Sansi ,&nbsp;Arjun Roy ,&nbsp;Richard Hartman","doi":"10.1016/j.neuropharm.2024.110275","DOIUrl":"10.1016/j.neuropharm.2024.110275","url":null,"abstract":"<div><h3>Background</h3><div>Evenamide, a glutamate modulator, is currently in phase 3 of development as add-on treatment to antipsychotics in patients with inadequate response or treatment-resistant schizophrenia. This study was designed to determine if patients with chronic schizophrenia inadequately responding to a second-generation antipsychotic would benefit from add-on treatment with evenamide at a dose of 30 mg <em>bid</em>.</div></div><div><h3>Methods</h3><div>Study 008A was a prospective, 4-week, randomized, double-blind, placebo-controlled study evaluating the safety, tolerability, and efficacy of oral doses of evenamide of 30 mg <em>bid</em> in patients with chronic schizophrenia treated at stable therapeutic doses of a second-generation antipsychotic. Outpatients aged ≥18 years, both males and females, with a diagnosis of schizophrenia (DSM-V), who had been receiving antipsychotics for at least 2 years at stable doses, but still symptomatic (PANSS 70–85, CGI-S 4–6, predominant positive symptoms), were eligible for the study. Patients were randomised equally to evenamide 30 mg or placebo, given <em>bid</em>, after completing a 21-day screening period. The primary outcome (change from baseline in PANSS total score) was assessed weekly, with the primary endpoint at 4 weeks.</div></div><div><h3>Results</h3><div>A total of 291 patients were enrolled, of which 11 (3·8%) discontinued prematurely, overall. Add-on treatment with evenamide was associated to a statistically significant (the absolute difference of the two treatment groups for the PANSS Total at Day 29, primary efficacy endpoint, was = 2·5 [p-value&lt;0.05] that is associated with a <em>Cohen's d</em> effect size = 0·33) and clinically meaningful benefit compared to placebo across all efficacy measures, and was well tolerated.</div></div><div><h3>Conclusion</h3><div>The demonstration of statistically significant and clinically meaningful benefit of evenamide, a glutamate modulator, as add-on treatment in patients with chronic schizophrenia inadequately responding to their second-generation antipsychotic may represent a new treatment paradigm for this population.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"266 ","pages":"Article 110275"},"PeriodicalIF":4.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872705","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":"Toluene is a cerebral artery constrictor acting via BK channels","authors":"Andrew A. Shaw,&nbsp;Jeffery D. Steketee,&nbsp;Anna N. Bukiya,&nbsp;Alex M. Dopico","doi":"10.1016/j.neuropharm.2024.110272","DOIUrl":"10.1016/j.neuropharm.2024.110272","url":null,"abstract":"<div><div>Acute intoxication by toluene usually follows intentional inhalation to achieve a “high”, which may lead to repeated use due to toluene's reinforcing properties. In both acute and chronic intoxication brain function is primarily affected. Neuronal and glial elements participate in toluene's reinforcing properties and chronic toxicity, yet the targets underlying acute toxicity remain unknown. Many signs of toluene's acute toxicity overlap with those of brain ischemia. Moreover, two studies in humans who abused toluene reveal brain hypoperfusion in middle cerebral artery (MCA) territories. Hypoperfusion, however, may result from either excessive vasoconstriction/increased vasodilation. Using rat and mouse models, we demonstrate that toluene at concentrations reached during recreational inhalation (8000 ppm) significantly decreases (−8%) MCA diameter <em>in vivo</em> in male and female animals. Using GC-MS, we determined toluene blood levels from inhalation (0.09–127 mM) and then show that &lt;1 mM toluene constricts <em>ex vivo</em>-pressurized MCA independently of endothelium. Toluene action is blunted by deletion of <em>KCNMA1</em>, which codes for BK channels, key regulators of MCA diameter, and upon selective channel blockade by 1 μM paxilline. Lastly, when applied onto an isolated membrane patch several minutes after patch-excision from the SM cell, submM toluene reduces mildly yet statistically significantly (P &lt; 0.05) both steady-state activity (−15%) and unitary current amplitude (−20%) of MCA myocyte BK channels. Thus, BK channels themselves and their immediate proteolipid microenvironment suffice for these drug actions. Collectively, data unveil a direct inhibition of MCA myocyte BK currents by intoxicating levels of toluene, which determines, or at least contributes to, MCA constriction by toluene levels reached during inhalation by humans who suffer acute brain intoxication.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"266 ","pages":"Article 110272"},"PeriodicalIF":4.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872706","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":"Paternal morphine alters offspring circulating beta-endorphin and corticosterone responses to oxycodone and cocaine","authors":"Sara B. Isgate,&nbsp;Kerri E. Budge,&nbsp;Elizabeth M. Byrnes,&nbsp;Fair M. Vassoler","doi":"10.1016/j.neuropharm.2024.110271","DOIUrl":"10.1016/j.neuropharm.2024.110271","url":null,"abstract":"<div><h3>Background</h3><div>The opioid epidemic is leading to increased opioid use in adolescent populations. A growing body of evidence suggests that taking opioids during adolescence can disrupt normal development and impact future offspring. This study investigates the impact of paternal morphine exposure during adolescence on the hypothalamic-pituitary-adrenal (HPA) axis and release of endorphins in the offspring.</div></div><div><h3>Methods</h3><div>Male rats were administered morphine once a day from postnatal day (PND)30–39 using an increasing dosing regimen (5–25 mg/kg/day increasing every other day). They were mated during adulthood to drug naïve females. Their offspring were assessed for circulating beta-endorphin (βE) and corticosterone levels on PND30 (a timepoint prior to puberty in both sexes) in response to an acute injection of saline, oxycodone (1 mg/kg, i.p.) or cocaine (10 mg/kg, i.p.). At PND60, naïve littermates were catheterized so that a within-subjects design could be implemented to measure βE and corticosterone in response to saline, oxycodone, or cocaine.</div></div><div><h3>Results</h3><div>In males, βE levels in the plasma were increased in Mor-F1 males compared to Sal-F1 males regardless of the acute injection. This elevation was observed at PND30 and PND60. There were no differences in female circulating βE. In terms of corticosterone, male Mor-F1 offspring had blunted corticosterone at PND30, but elevated corticosterone in response to oxycodone at PND60. The females also tended towards lower corticosterone prior to puberty but had significantly elevated levels of circulating corticosterone following an acute cocaine injection.</div></div><div><h3>Conclusion</h3><div>Paternal morphine exposure during adolescence induces sex- and drug-specific changes in secreted hormone responses in offspring. The alterations in βE and corticosterone levels suggest mechanisms through which adolescent opioid exposure can impact endocrine functions of future offspring. These findings contribute to the understanding of intergenerational transmission of substance use effects.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"265 ","pages":"Article 110271"},"PeriodicalIF":4.6,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854727","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":"Serotonin 5-HT1A receptor biased agonists: The challenge of translating an innovative neuropharmacological concept into therapeutics","authors":"Luc Zimmer ,&nbsp;Adrian Newman-Tancredi","doi":"10.1016/j.neuropharm.2024.110267","DOIUrl":"10.1016/j.neuropharm.2024.110267","url":null,"abstract":"<div><div>Serotonin 5-HT_1A receptor agonists are prime candidates for CNS drug discovery due to their involvement physiological and pathological processes relevant to neurology and psychiatry. However, the lack of target specificity of many previously characterized agonists has long been a barrier to pharmacological and therapeutic progress. Some of the obstacles may be overcome through the recent concept of biased agonism, which has attracted considerable attention to the development of novel chemical entities at 5-HT, and particularly 5-HT_1A receptors, by specifically targeting intracellular signalling pathways that may themselves be linked to specific brain regions and therapeutic indications. There is now abundant translational data demonstrating distinct molecular and functional pharmacological signatures between different 5-HT_1A receptor agonists, opening new opportunities for research in neurology and psychiatry. Nevertheless, important limitations need to be overcome, including understanding the precise molecular basis for biased agonism, the need for improved translatable models, and the currently limited clinical data on biased agonists. Here, we review the current limits of our knowledge of 5-HT_1A receptor biased agonists and the limitations of available pharmacological tools, counterbalanced by the translational possibilities and therapeutic perspectives opened by novel, highly selective 5-HT1A receptor drug-candidates.</div><div>This article is part of the Special Issue on \"Ligand Bias\".</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"265 ","pages":"Article 110267"},"PeriodicalIF":4.6,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838312","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":"Short chain fatty acids mediates complement C1q pathway alleviation of perioperative neurocognitive disorders","authors":"Xiang Liu ,&nbsp;Xiaona Tan ,&nbsp;Yaozong Yu ,&nbsp;Junfang Niu ,&nbsp;Bo Zhao ,&nbsp;Qiujun Wang","doi":"10.1016/j.neuropharm.2024.110266","DOIUrl":"10.1016/j.neuropharm.2024.110266","url":null,"abstract":"<div><div>Perioperative neurocognitive disorders (PND) is one of the most common postoperative complications, which can lead to a harmful impact on self-dependence, longer hospital stays, increased medical costs, morbidity, and mortality amongst older adults. Microglia can modulate synapse elimination involved in the complement component protein 1q (C1q) pathway to induce cognitive dysfunction, which is significantly improved by short chain fatty acids (SCFAs) treatment. Here we investigate the effects of SCFAs treatment on PND via mediating C1q complement pathway. High-throughput sequencing of 16S rDNA from fecal samples of male SD rats was applied to assess the changes in gut microbiota. Fecal microbiota transplantation (FMT) was performed to investigate whether gut microbiota from PND rats could alter cognitive impairment. The blood from the rat tail vein was collected to measure the SCFAs concentrations. Hippocampal and brain tissue samples were obtained to perform Western blots, Golgi and immunofluorescence staining. Primary microglia treated with SCFAs or Histone deacetylase inhibitor were cultured to measure microglial activation states and the expression of acetylated histone. The 16S rDNA sequencing results showed that PND rats had the significant changes in the species diversity of the gut microbiota and the metabolite of specifc species. Gut microbiota from PND rats could alter spatial learning and memory, and meanwhile, the changed SCFAs concentrations in plasma were involved. The synapse elimination in PND rats was strikingly reversed by SCFAs treatment involved in modulation complement C1q via suppressing neuroinflammation. This suggests that a link between gut microbiota dysbiosis and cognitive function impairment is involved in synapse elimination via mediating complement C1q pathway. SCFAs treatment can alleviate PND, the mechanisms of which may be associated with regulating complement C1q pathway.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"265 ","pages":"Article 110266"},"PeriodicalIF":4.6,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838316","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":"Insights into the neurobiology of weight loss after bariatric surgery and GLP-1R agonists","authors":"Tyler M. Cook,&nbsp;Kelly N.Z. Fuller,&nbsp;Darleen A. Sandoval","doi":"10.1016/j.neuropharm.2024.110269","DOIUrl":"10.1016/j.neuropharm.2024.110269","url":null,"abstract":"<div><div>Obesity and its related complications are growing in prevalence worldwide, with increasing impact to individuals and healthcare systems alike. Currently, the leading treatment approaches for effective and sustained weight loss are bariatric surgery and gut peptide therapeutics. At a high level, both treatment strategies work by hijacking gut-brain axis signaling to reduce food intake. However, we predict that each modality has distinct neuronal mechanisms that are responsible for their success and complications. This review compares the neurobiology of feeding behavior between these two weight loss strategies via a discussion of both clinical and pre-clinical data. The most compelling evidence points to signaling within the hindbrain, hypothalamus, and reward circuits contributing to weight loss. Considerations for treatment, including differing complications between the two treatment approaches, will also be discussed. Based on the data, we pose the hypothesis that these two interventions are acting via distinct mechanisms to induce weight loss. Both interventions have variable degrees of weight loss across the patient population, thus, understanding these distinct mechanisms could help drive individualized medicine to optimize weight loss.</div><div>This article is part of the Special Issue on \"Food intake and feeding states\".</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"265 ","pages":"Article 110269"},"PeriodicalIF":4.6,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829529","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":"Subanesthetic propofol alleviates chronic stress-induced anxiety by enhancing VTADA neurons’ activity","authors":"Shaolei Jiang ,&nbsp;Dengyun Ge ,&nbsp;Bo Song ,&nbsp;Xiaofei Deng ,&nbsp;Zhongdong Liu ,&nbsp;Jian He ,&nbsp;Jing Sun ,&nbsp;Zhi Zhu ,&nbsp;Zhiqiang Meng ,&nbsp;Yingjie Zhu","doi":"10.1016/j.neuropharm.2024.110264","DOIUrl":"10.1016/j.neuropharm.2024.110264","url":null,"abstract":"<div><div>Anxiety, a common mental disorder, imposes significant clinical and economic burdens. Previous studies indicate that propofol has anxiolytic effects at anesthetic doses. However, the risks associated with general anesthesia limit its application in anxiety treatment. The feasibility of using subanesthetic doses of propofol to alleviate chronic stress-induced anxiety and the underlying neural mechanisms remain unknown. Here, we found that subanesthetic dose (20 mg/kg and 40 mg/kg) of propofol alleviated anxiety-like behaviors induced by chronic unpredictable mild stress (CUMS) in mice, and the anxiolytic effects were maintained for at least 6 h. <em>In vivo</em> calcium imaging study showed that propofol significantly enhanced Ca²⁺ signals in ventral tegmental area dopaminergic (VTA^DA) neurons. Whole-cell patch-clamp recordings confirmed that subanesthetic propofol increased the excitability of VTA^DA neurons while inhibiting VTA GABAergic (VTA^GABA) neurons. Propofol suppressed spontaneous inhibitory postsynaptic currents (sIPSCs) in VTA^DA neurons, accompanied by a decline in the ability of GABAergic neurons to transmit inhibitory signals. These findings suggests that a subanesthetic dose of propofol enhances the excitability of VTA^DA neurons through disinhibition, demonstrating its potential for the treatment of CUMS-associated anxiety-like behaviors.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"265 ","pages":"Article 110264"},"PeriodicalIF":4.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829530","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}