Neuropharmacology最新文献

{"title":"Electrophysiological analysis of paraventricular thalamic neurons co-expressing kappa and mu opioid receptors","authors":"E.J. Kuijer ,&nbsp;S.J. Bailey ,&nbsp;D.J. Heal ,&nbsp;S. Smith ,&nbsp;S. Wonnacott ,&nbsp;C.P. Bailey","doi":"10.1016/j.neuropharm.2025.110407","DOIUrl":"10.1016/j.neuropharm.2025.110407","url":null,"abstract":"<div><div>The paraventricular thalamus (PVT) is a central node in the integration of stress- and reward-related information that may serve as a pivotal site for opioid receptors to exert their effects. Kappa opioid receptors (KOPrs) and mu opioid receptors (MOPrs) have dissociable and opposing roles in circuits of stress and reward. Interestingly, both are highly expressed in the PVT, however it is not known how aversive KOPr and rewarding MOPr signalling converges to dictate PVT activity and, by proxy, whole brain effects. We have investigated the function of KOPrs and MOPrs in single PVT neurons using whole-cell voltage-clamp recordings in brain slices from female and male mice (4–8 weeks). The majority of PVT neurons (69 %) co-expressed KOPr and MOPr. Activation of either receptor produced outward K⁺ currents, with no age and sex differences. In neurons co-expressing both opioid receptors, the MOPr-induced K⁺ current reversed around the theoretical equilibrium potential, whilst the KOPr current did not reverse at any holding potential tested. Furthermore, investigation of apparent inward currents produced by MOPr inverse agonists suggested the presence of tonically active MOPrs, predominantly in the anterior PVT. Activation of both KOPrs and MOPrs decreased glutamatergic input to PVT neurons by around 40 %, whereas only KOPr activation decreased GABAergic input, by 46 %. Together these data suggest that the balance of activation of KOPrs and MOPrs in the PVT plays a critical role in integrating stress- and reward-related signals.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"272 ","pages":"Article 110407"},"PeriodicalIF":4.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616433","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":"Side effects of microdosing lysergic acid diethylamide and psilocybin: A systematic review of potential physiological and psychiatric outcomes","authors":"Stefan Modzelewski ,&nbsp;Anna Stankiewicz ,&nbsp;Napoleon Waszkiewicz ,&nbsp;Kacper Łukasiewicz","doi":"10.1016/j.neuropharm.2025.110402","DOIUrl":"10.1016/j.neuropharm.2025.110402","url":null,"abstract":"<div><h3>Objective</h3><div>Psychedelics are gaining renewed attention, especially through the practice of microdosing, where low doses are taken regularly. Microdosing lysergic acid diethylamide (LSD) and psilocybin is used by both healthy individuals and those with mental health conditions to improve daily functioning, reduce anxiety, and enhance mood and cognition. However, there is limited information about the side effects of this practice. This review aimed to collect and characterize the side effects of psychedelic microdosing.</div></div><div><h3>Methods</h3><div>We conducted a systematic review of original papers from PubMed, Web of Science, and Scopus (accessed August 03, 2024) that reported side effects of microdosing LSD and psilocybin. Non-English papers, non-original studies, studies without typical microdosing doses, or those lacking descriptions of side effects were excluded. Our methodology has been developed in accordance with PRISMA guidelines. Because side effects were assessed heterogeneously in these papers, we did not perform a bias evaluation.</div></div><div><h3>Results</h3><div>We included 31 studies, 15 of which we classified as laboratory studies with higher quality evidence, and 14 studies with lower quality evidence, as well as 2 clinical cases. Side effects were typically dose-dependent, mild, and short-lived. Common adverse effects included increased blood pressure, anxiety, and cognitive impairment.</div></div><div><h3>Discussion</h3><div>This review is limited by the heterogeneity in reporting side effects and the short duration of many studies. Future studies should transparently and systematically present a description of side effects.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"271 ","pages":"Article 110402"},"PeriodicalIF":4.6,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586389","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":"Neurotransmitter imbalance and amygdala synaptic plasticity in lumbar disc herniation-induced chronic pain and related emotional Disturbances:A multi-omics analysis","authors":"Zhenyu Huang ,&nbsp;Haibo Tan ,&nbsp;Yuanfei Fu ,&nbsp;Huanxin Xie ,&nbsp;Huangsheng Tan ,&nbsp;Kun Gao ,&nbsp;Hongkan Lou","doi":"10.1016/j.neuropharm.2025.110405","DOIUrl":"10.1016/j.neuropharm.2025.110405","url":null,"abstract":"<div><div>Chronic pain due to lumbar disc herniation (LDH) significantly impairs quality of life and is often accompanied by emotional disturbances, such as anxiety and depression. Despite the recognition of these comorbidities, the underlying neural mechanisms remain unclear. This study investigates the role of neurotransmitter imbalances and key regulatory molecules in LDH-induced chronic pain and related emotional disturbances, with a focus on synaptic plasticity in the amygdala. A rat model of LDH was developed using male Sprague-Dawley rats. Behavioral assessments were conducted to evaluate pain hypersensitivity, anxiety, and depression-like behaviors. Cerebrospinal fluid (CSF) metabolomics and amygdala transcriptomics were employed to analyze neurotransmitter profiles and gene expression. In vitro experiments were conducted to explore the role of PRKCG in synaptic plasticity. Behavioral tests showed significant pain hypersensitivity and anxiety- and depression-like behavior in LDH rats. Metabolomic analysis revealed altered levels of glutamate and γ-aminobutyric acid (GABA) in the CSF, indicating neurotransmitter imbalances. Transcriptomic profiling identified changes in genes related to synaptic plasticity, including PRKCG. PRKCG knockdown led to reduced CAMKII phosphorylation and GRIA1 expression, supporting its role in modulating synaptic plasticity. This study provides evidence that neurotransmitter imbalances and alterations in synaptic plasticity within the amygdala may contribute to the persistence of chronic pain and associated emotional disturbances in LDH. PRKCG may represent a novel therapeutic target for treating both chronic pain and related emotional disturbances.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"271 ","pages":"Article 110405"},"PeriodicalIF":4.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586388","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":"Role of endocannabinoid neurotransmission in the insular cortex on cardiovascular, autonomic and behavioral responses evoked by acute restraint stress in rats","authors":"Ivaldo J.A. Belem-Filho ,&nbsp;Ana C.V. Godoy ,&nbsp;Cristiane Busnardo ,&nbsp;Alana T. Frias ,&nbsp;Helio Zangrossi Jr. ,&nbsp;Bruno Del Bianco Borges ,&nbsp;Ana C.F. Herval ,&nbsp;Fernando M.A. Correa ,&nbsp;Carlos C. Crestani ,&nbsp;Fernando H.F. Alves","doi":"10.1016/j.neuropharm.2025.110404","DOIUrl":"10.1016/j.neuropharm.2025.110404","url":null,"abstract":"<div><div>This study aimed to investigate the role of endocannabinoid mechanisms present within the insular cortex (IC) on cardiovascular, autonomic and anxiogenic-like responses evoked by an acute session of restraint in rats. For this, bilateral guide cannulas directed to the IC were implanted in male Wistar rats for intrabrain microinjection of the selective CB₁ receptor antagonist AM251, the selective TRPV1 receptor antagonist capsazepine, the fatty acid amide hydrolase (FAAH) inhibitor URB597 or the monoacylglycerol lipase (MAGL) inhibitor JZL184. The effects of pharmacological treatments were evaluated on restraint-evoked increases in blood pressure and heart rate, sympathetically-mediated cutaneous vasoconstriction and in delayed anxiogenic-like effect assessed 24h after stress exposure in the elevated plus maze (EPM) and open field (OF). We observed that acute restraint stress decreased the exploration of both EPM open arms and OF center region in animals treated with vehicle into the IC, thus indicating an anxiogenic-like effect. Inhibition of MAGL within the IC evoked by local treatment with JZL184 avoided the restraint-evoked anxiogenic effect. IC treatment with JZL184 also attenuated the tachycardia during restraint. The other pharmacological treatments did not modify the cardiovascular, autonomic and behavioral responses evoked by restraint. Taken together, these findings suggest that endocannabinoid neurotransmission in the IC, potentially acting through the endocannabinoid 2-arachidonoylglycerol, plays an inhibitory role in both tachycardia and anxiogenic-like effect evoked by stressful events.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"271 ","pages":"Article 110404"},"PeriodicalIF":4.6,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563665","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":"Cuprizone-induced demyelination provokes abnormal intrinsic properties and excitatory synaptic transmission in the male mouse anterior cingulate cortex","authors":"Ryo Kawabata ,&nbsp;Shinji Yamamoto ,&nbsp;Nana Kamimura ,&nbsp;Ikuko Yao ,&nbsp;Keisuke Yoshikawa ,&nbsp;Kohei Koga","doi":"10.1016/j.neuropharm.2025.110403","DOIUrl":"10.1016/j.neuropharm.2025.110403","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). Demyelination in the CNS provokes hyperalgesia, negative emotions, and/or cognitive impairment. Cuprizone (CPZ)-induced demyelination is a major demyelinating disease model for rodents. The anterior cingulate cortex (ACC) is a brain region that is responsible for higher brain functions related to MS symptoms. However, little is known whether CPZ exposure induces demyelination in the ACC coincides with changes to intrinsic neuron properties and synaptic transmission. In this study, we first examined if CPZ exposure induces demyelination in the male mouse ACC. CPZ exposure induced demyelination in the ACC and decreased body weight. In addition, demyelination altered intrinsic properties and excitatory synaptic transmission in layer II/III pyramidal neurons from the ACC as indicated by whole-cell patch-clamp in brain slice preparations. CPZ exposure decreased the frequency of action potentials due to increasing rheobase. At the synapse level, CPZ exposure also suppressed evoked excitatory synaptic transmission to the ACC. Finally, CPZ exposure also changed the kinetics of AMPA and NMDA receptors. These results suggest that CPZ exposure induces demyelination in the ACC coinciding with changes in intrinsic properties, action potentials and excitatory synaptic transmission.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"271 ","pages":"Article 110403"},"PeriodicalIF":4.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552644","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 novel ferroptosis inhibitor phenothiazine derivative reduces cell death and alleviates neurological impairments after cerebral hemorrhage","authors":"Bing-Qiao Wang ,&nbsp;Yu-Fan Ma ,&nbsp;Ru Chen ,&nbsp;Guo-Qing Zhang ,&nbsp;Qi Xie ,&nbsp;Chang-Xiong Gong ,&nbsp;Xiao-feng Cheng ,&nbsp;Qin Zhang ,&nbsp;Yuan Zhao ,&nbsp;Shuang Zhang ,&nbsp;Zhao-You Meng ,&nbsp;Yi-Liang Fang ,&nbsp;Cheng-Kang He ,&nbsp;Yan-Jie Huang ,&nbsp;Sen Lin ,&nbsp;Qing-Wu Yang","doi":"10.1016/j.neuropharm.2025.110399","DOIUrl":"10.1016/j.neuropharm.2025.110399","url":null,"abstract":"<div><div>The precise etiology of brain injury induced by intracerebral hemorrhage (ICH) remains unclear. Currently, there are no effective therapeutic options available to slow down or prevent the progression of the disease. An increasing body of evidence suggests that ferroptosis plays a significant role in the development of injury related to ICH. Furthermore, pharmacological inhibition of ferroptosis has been identified as a promising therapeutic target for ICH injury. The compound 2-(1-(4-(4-methylpiperazin-1-yl)phenyl)ethyl)-10H-phenothiazine (compound-51), a derivative of promethazine, has been demonstrated to exhibit anti-ferroptosis and antioxidant properties. The aim of this study is to investigate the role and mechanism of action of compound-51 in a rat model of ICH. The <em>in vivo</em> experiments demonstrated that compound-51 significantly alleviated neurological impairments, reduced brain edema, and decreased hematoma volume. At the cellular level, compound-51 was observed to significantly enhance cellular survival and inhibit ferroptosis. Furthermore, compound-51 demonstrated a more pronounced therapeutic effect than Fer-1, without causing any injury to the heart, kidney, or liver. <em>In vitro</em> experiments demonstrated that compound-51 significantly increased cell viability and intracellular GPX4 levels, while reducing lipid peroxidation and oxidized glutathione levels. Collectively, these findings indicate that compound-51 exhibits a pronounced anti-ferroptosis function and alleviates neurological impairments in an ICH model, suggesting its potential as a new therapeutic agent for the treatment of ICH.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"271 ","pages":"Article 110399"},"PeriodicalIF":4.6,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552643","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":"Corrigendum to “Enriched environment mitigates cognitive impairment in pre-adolescent mice following repeated neonatal sevoflurane exposure by reducing TTBK1 expression and Tau phosphorylation” [Neuropharmacology 268 (2025) 110327]","authors":"Yang Yu ,&nbsp;Jiafeng Yu ,&nbsp;Banglin Wu ,&nbsp;Yuanlin Wang ,&nbsp;Yun Li ,&nbsp;Yongyan Yang ,&nbsp;Yonghao Yu ,&nbsp;Jingyu Feng","doi":"10.1016/j.neuropharm.2025.110388","DOIUrl":"10.1016/j.neuropharm.2025.110388","url":null,"abstract":"","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"271 ","pages":"Article 110388"},"PeriodicalIF":4.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537455","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":"Pro-inflammatory mediators sensitise transient receptor potential melastatin 3 cation channel (TRPM3) function in mouse sensory neurons","authors":"Javier Aguilera-Lizarraga,&nbsp;Tony K. Lim,&nbsp;Luke A. Pattison,&nbsp;Luke W. Paine,&nbsp;David C. Bulmer,&nbsp;Ewan St John Smith","doi":"10.1016/j.neuropharm.2025.110391","DOIUrl":"10.1016/j.neuropharm.2025.110391","url":null,"abstract":"<div><div>Pro-inflammatory mediators can directly activate pain-sensing neurons, known as nociceptors. Additionally, these mediators can sensitise ion channels and receptors expressed by these cells through transcriptional and post-translational modulation, leading to nociceptor hypersensitivity. A well-characterised group of ion channels that subserve nociceptor sensitisation is the transient receptor potential (TRP) superfamily of cation channels. For example, the roles of TRP channels vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) in nociceptor sensitisation and inflammatory pain have been extensively documented. In the case of TRP melastatin 3 (TRPM3), however, despite the increasing recognition of this channel's role in inflammatory pain, the mediators driving its sensitisation during inflammation remain poorly characterised. Here, using Ca²⁺ imaging, we found that an inflammatory soup of bradykinin, interleukin 1β (IL-1β) and tumour necrosis factor α (TNFα) sensitised TRPM3 function in isolated mouse sensory neurons; IL-1β and TNFα, but not bradykinin, independently potentiated TRPM3 function. TRPM3 expression and translocation to the membrane remained unchanged upon individual or combined exposure to these inflammatory mediators, which suggests that post-translational modification might occur. Finally, using the complete Freund's adjuvant-induced model of knee inflammation, we found that systemic pharmacological blockade of TRPM3 does not alleviate inflammatory pain (as assessed through evaluation of digging behaviour and dynamic weight bearing), which contrasts with previous reports using different pain models. We propose that the nuances of the immune response may determine the relative contribution of TRPM3 to nociceptive signalling in different neuro-immune contexts. Collectively, our findings improve insight into the role of TRPM3 sensitisation in inflammatory pain.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"271 ","pages":"Article 110391"},"PeriodicalIF":4.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528660","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":"Maternal N-acetylcysteine supplementation in lactation ameliorates metabolic and cognitive deficits in adult offspring exposed to maternal obesity","authors":"Eden Yonatan ,&nbsp;Orya Noa Shukha ,&nbsp;Idit Golani ,&nbsp;Saher Abu-ata ,&nbsp;Yaseen Awad-Igbaria ,&nbsp;Nizar Khatib ,&nbsp;Yuval Ginsberg ,&nbsp;Eilam Palzur ,&nbsp;Ron Beloosesky ,&nbsp;Alon Shamir","doi":"10.1016/j.neuropharm.2025.110390","DOIUrl":"10.1016/j.neuropharm.2025.110390","url":null,"abstract":"<div><div>Maternal obesity in pregnancy and lactation is linked to metabolic disturbances and neurodevelopmental problems in offspring, increasing the risk of psychiatric disorders in adulthood. We proposed that maternal N-acetyl cysteine (NAC) supplementation during lactation, a critical period for neurodevelopment, potentially protects offspring from developing cognitive impairment in adulthood. Fifteen young female ICR mice were randomly allocated to different experimental groups: high-fat diet (HFD; 60.3% fat before mating, during pregnancy and lactation), HFD-NAC of 300 mg/kg/day during lactation, CD (high-fat diet before mating, during pregnancy, and regular chow control diet of 8.2% fat during lactation), CD-NAC of 300 mg/kg/day during lactation and control group consuming regular chow diet. The serum inflammatory markers of the offspring were evaluated post-weaning, while metabolic markers, microglial density, and cognitive performance were assessed in adulthood using the novel Object Recognition and Morris Water Maze tests. Our results demonstrate maternal obesity during gestation and lactation increased body weight, hepatic steatosis, and microglial cell density in the dentate gyrus (DG) and cortex. Furthermore, these offspring exhibited reduced spatial learning abilities in adulthood, regardless of sex. However, maternal NAC administration during lactation and maternal diet intervention significantly reduced brain microglial density and improved both male and female offspring metabolic profiles. More importantly, NAC supplementation during lactation, regardless of maternal diet, enhanced male offspring's learning ability in adulthood. Our findings indicate that administering NAC to obese mothers during the critical lactation period may offer protection against metabolic disturbances and cognitive deficits in adult offspring previously exposed to maternal obesity.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"271 ","pages":"Article 110390"},"PeriodicalIF":4.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537464","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":"β-2 agonist and antagonist adrenoceptors induce neuroprotection in a progressive model of parkinsonism","authors":"Auderlan M. de Gois ,&nbsp;José M.M. Bispo ,&nbsp;Edson R. Santos ,&nbsp;Marina F. Souza ,&nbsp;João E.C. Melo ,&nbsp;Mylaine S. Mendonça ,&nbsp;Thiago H. Almeida-Souza ,&nbsp;Enilton A. Camargo ,&nbsp;Katty A.A.L. Medeiros ,&nbsp;Pollyana C. Leal ,&nbsp;Heitor F. Santos ,&nbsp;Lívia C.R.F. Lins ,&nbsp;Alessandra M. Ribeiro ,&nbsp;Regina H. Silva ,&nbsp;José R. Santos","doi":"10.1016/j.neuropharm.2025.110386","DOIUrl":"10.1016/j.neuropharm.2025.110386","url":null,"abstract":"<div><div>Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive dopaminergic dysfunction in the nigrostriatal pathway, as well as alterations in other monoamines systems. Research indicates that the use of β-adrenergic agonist and antagonists influences the risk of PD. This study evaluated the effects of salbutamol and propranolol on motor and neurochemical parameters in a progressive model of parkinsonism induced by reserpine (RES). Male Wistar rats were chronically treated with 12 subcutaneous injections of RES (0,1 mg/kg) given every other day for 24 days. From the 16th day onwards, the animals were daily treated with salbutamol (5 mg/kg) or propranolol (20 mg/kg) intraperitoneally for 8 days. Salbutamol reduced the motor deficit caused by RES in the catalepsy test, while propranolol reduced the damages caused by RES in the vacuous chewing movements evaluation. In immunohistochemical analysis both salbutamol and propranolol prevented dopaminergic damage in the substantia nigra pars compacta (SNpc), ventral tegmental area (VTA), striatum and noradrenergic damage in locus coeruleus (LC). In addition, salbutamol and propranolol prevented the increase in α-synuclein immunoreactivity caused by RES in the substantia nigra pars reticulata (SNr), striatum, prefrontal cortex (mPFC) and hippocampus. These data show that salbutamol and propranolol promote neuroprotective effects against reserpine-induced parkinsonism. However, further studies are needed to understand the mechanisms involved in β-adrenoceptors role in PD development.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"271 ","pages":"Article 110386"},"PeriodicalIF":4.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537466","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}