Neuropharmacology最新文献

{"title":"Serotonin 2A (5-HT2A) receptor as evolving biological target: function, structure, ligands and role in the therapy of neuropsychiatric diseases","authors":"Monika Fryc,&nbsp;Daria Kluzik,&nbsp;Anna Czopek,&nbsp;Jakub Jończyk,&nbsp;Agnieszka Zagórska","doi":"10.1016/j.neuropharm.2025.110622","DOIUrl":"10.1016/j.neuropharm.2025.110622","url":null,"abstract":"<div><div>The serotonin 5-HT_2A receptor is a G-protein-coupled receptor that plays a critical role in numerous physiological processes within the central nervous system. While it is essential for normal neurobiological function, dysregulation or aberrant signaling of the 5-HT_2A receptor has been implicated in the pathophysiology of various neuropsychiatric disorders. This review provides a comprehensive overview of the 5-HT_2A receptor, including its structure, function, ligand interactions, and therapeutic potential. Its molecular structure is detailed, with key binding domains highlighted that facilitate interactions with agonists, antagonists, and inverse agonists, influencing receptor activation and intracellular signaling pathways. The sites of 5-HT_2A receptor expression in both the central and peripheral nervous systems are also presented, and ligands are classified based on their interactions with the receptor. The receptor's role as a focal point in the treatment of psychiatric disorders such as schizophrenia and depression is examined, with emphasis placed on its modulation by atypical antipsychotics and emerging psychedelic-based therapies. Furthermore, its involvement in functional selectivity, biased agonism, and interactions with dopaminergic and glutamatergic systems is explored. Recent advancements in non-hallucinogenic 5-HT_2A receptor agonists and inverse agonists are also discussed, highlighting their potential for therapeutic intervention with improved safety profiles. The insights provided in this review contribute to a deeper understanding of 5-HT_2A receptors' role in neuropsychiatric disorders and support ongoing drug development efforts to optimize receptor-targeted therapies.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"279 ","pages":"Article 110622"},"PeriodicalIF":4.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768807","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":"Age- and estrous-dependent effects of psilocybin in rats","authors":"A.L. Zylko ,&nbsp;R.J. Rakoczy ,&nbsp;B.F. Roberts ,&nbsp;M. Wilson ,&nbsp;A. Powell ,&nbsp;A. Page ,&nbsp;M. Heitkamp ,&nbsp;D. Feist ,&nbsp;J.A. Jones ,&nbsp;M.S. McMurray","doi":"10.1016/j.neuropharm.2025.110619","DOIUrl":"10.1016/j.neuropharm.2025.110619","url":null,"abstract":"<div><div>Psilocybin, a psychedelic compound in “magic” mushrooms, has promise as a novel treatment for psychiatric disorders, many of which are more prevalent in females and have onsets during adolescence. However, there is a lack of research about how factors such as sex and age affect responses to psilocybin, as well as potential safety concerns with developmental exposure. The primary objectives of this preclinical study were to determine if psilocybin-induced head twitch responses differ between adolescent and adult rats, and if estrous phase contributes to variation in female head twitch responses. Secondarily, this study sought to determine if treatment with psilocybin during adolescence has long-term effects on anxiety-associated behaviors and behavioral flexibility. Results showed that 1 mg/kg intragastric psilocybin failed to elicit head twitch responses in adolescents (P35 and P45) but elicited robust responses in adult rats. Further, adolescent psilocybin exposure did not cause long-term differences in performance on the elevated zero maze or probabilistic reversal learning tasks. Lastly, adult females in diestrus showed increased head twitch responses after 1 mg/kg psilocybin compared to females in proestrus. Collectively, these results highlight the existence of age- and sex-dependent differences in the effects of psychedelics, while finding no long-term effects on selected behaviors after adolescent exposure. These findings have implications on psychedelic study design, emphasizing the need for inclusive research considering age, sex, and hormonal status.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"279 ","pages":"Article 110619"},"PeriodicalIF":4.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760603","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":"Low-molecular weight protamine enhances neuroprotection and remyelination by mitigating chondroitin sulfate proteoglycan inhibition in models of demyelination","authors":"Tapani K. Koppinen ,&nbsp;Carolina R. Reyes ,&nbsp;Liam Beckett ,&nbsp;Jinhan Nam ,&nbsp;Tuomas A.E. Kallionpää ,&nbsp;Saila Medina Leskinen ,&nbsp;Nadine Huber ,&nbsp;Annakaisa Haapasalo ,&nbsp;Francisco J. Rivera ,&nbsp;Merja H. Voutilainen ,&nbsp;Heikki Rauvala","doi":"10.1016/j.neuropharm.2025.110618","DOIUrl":"10.1016/j.neuropharm.2025.110618","url":null,"abstract":"<div><div>Chondroitin sulfate proteoglycans (CSPGs) are inhibitory molecules deposited in the extracellular matrix of lesions in multiple sclerosis (MS). CSPGs maintain ongoing inflammatory processes and prevent oligodendrocyte progenitor cell (OPC) differentiation, resulting in impaired remyelination and chronic pathology in MS. Here, we profile low-molecular weight protamine (LMWP) as a small, positively charged peptide that binds to the negatively charged inhibitory sections of CSPGs. We show that LMWP overcomes CSPG inhibition of OPC differentiation and increases remyelination following toxin-based focal demyelination. Moreover, LMWP ameliorates disease progression in experimental autoimmune encephalomyelitis (EAE) model. LMWP is blood brain barrier-penetrant, and peripheral administration in EAE mice results in significantly lowered concentrations of serum neurofilament light-chain. Additionally, tissue analyses show increased myelin thickness and a reduction in axonal degeneration with LMWP treatment in EAE mice, supporting its role as a neuroprotective compound. Finally, LMWP reduces microgliosis and fibrosis in EAE, most likely, favoring tissue repair. Thus, LMWP supports remyelination as well as neuroprotection resulting in a promising strategy for the treatment of demyelinating disease, such as MS.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"279 ","pages":"Article 110618"},"PeriodicalIF":4.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749513","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":"Comparative effectiveness of moderate treadmill training and venlafaxine treatment on long-lasting brain changes induced by prenatal dexamethasone exposure","authors":"Katarzyna Głombik ,&nbsp;Magdalena Kukla-Bartoszek ,&nbsp;Maciej Suski ,&nbsp;Katarzyna Curzytek ,&nbsp;Beata Grygier ,&nbsp;Agnieszka Basta-Kaim","doi":"10.1016/j.neuropharm.2025.110604","DOIUrl":"10.1016/j.neuropharm.2025.110604","url":null,"abstract":"<div><div>Prenatal exposure to dexamethasone (DEX) is known to induce long-term behavioral and molecular impairments. This research investigated whether moderate physical exercise (treadmill running) and venlafaxine administration, or their combination, applied in early adulthood, could modulate the behavioral and brain molecular alterations induced by prenatal DEX exposure in Sprague-Dawley male rats. It was demonstrated that both exercise and venlafaxine treatment ameliorated deficits in memory, depressive-like behavior, and anxiety-like behavior. Subsequent proteomic analysis of the frontal cortex revealed significant modulation in the proteome following each intervention. Analysis disclosed convergent effects of all three interventions, notably the upregulation of LYAR and downregulation of KLHL36. Increased LYAR expression may counteract DEX-induced ribosomal inhibition, while reduced KLHL36 aligns with potential stress resilience modulation. Shared protein changes between exercise and venlafaxine implicated pathways governing learning, regulation of neurotransmitter levels and their metabolism, and cell-cell organization. Combined treatment uniquely impacted 164 proteins involved in 44 distinct biological pathways, which suggests that joint use of training and venlafaxine has a pleiotropic effect. Among the altered pathways besides behavior, cognition, and memory were glycerophospholipid and arachidonic acid metabolism, which potentially influence neuronal membrane integrity and synaptic function, as well as exocytosis and MAPK signaling pathways. Notably, among the investigated mitochondrial proteins, HIGD1a exhibited a consistent pattern of upregulated expression across all three experimental treatment groups, suggesting altered mitochondrial function and antioxidant defense by the treatments used.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"279 ","pages":"Article 110604"},"PeriodicalIF":4.6,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144739663","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":"In vitro and in vivo pharmacological characterization of fentanyl analogs","authors":"Samuel Obeng ,&nbsp;Kyle R. Urquhart ,&nbsp;Saki Fukuda ,&nbsp;Victoria L.C. Pallares ,&nbsp;Lance R. McMahon ,&nbsp;William E. Fantegrossi ,&nbsp;Takato Hiranita","doi":"10.1016/j.neuropharm.2025.110603","DOIUrl":"10.1016/j.neuropharm.2025.110603","url":null,"abstract":"<div><div>Opioid overdose is the leading cause of unintentional drug-related deaths in the United States (US), largely due to the use of illicitly manufactured synthetic opioids like fentanyl and its analogs. The pharmacological properties of novel fentanyl analogs are largely unknown. Thus, this study characterized opioid-like activities of six novel fentanyl analogs (acryl fentanyl, β-hydroxythio fentanyl, cyclohexyl fentanyl, 4-fluoroisobutyrly fentanyl, furanyl fentanyl, and tetrahydrofuranyl fentanyl) <em>in vitro</em> and <em>in vivo</em>, in comparison to morphine and fentanyl. In radioligand binding assays using [³H](D-Ala², <em>N</em>-MePhe⁴, Gly-ol)-enkephalin (DAMGO) and the human <em>mu</em> opioid receptor (MOR) stably expressed in Chinese hamster ovary cells, all test substances except cyclohexyl fentanyl exhibited sub-nanomolar affinity for MOR. Furthermore, assessments of stimulation of [³⁵S]guanosine 5′-O-[γ-thio]triphosphate (GTPγS) binding at the MOR indicated that all test substances functioned as MOR agonists (E_max in % of DAMGO: 69.8–105), except for cyclohexyl fentanyl (13.3 %). In the warm water tail withdrawal procedure (55 °C) using male CD1 mice, cumulative injections of each test substance (S.C., N = 8 per group) produced dose-dependent increases in tail-flick latency (ED₅₀s: 0.158–3.18 mg/kg), which were blocked by the opioid receptor antagonist naltrexone. The antinociceptive potencies of each test substance were similar to or less than that of fentanyl (ED₅₀: 0.122 mg/kg). Additional <em>in vivo</em> studies using morphine discrimination, locomotor activity, and assessments of precipitated withdrawal further corroborated the MOR effects of these fentanyl analogs. Importantly, all the analogs produced morphine-like subjective effects suggesting that these compounds may have abuse liabilities similar to morphine.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"279 ","pages":"Article 110603"},"PeriodicalIF":4.6,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732438","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":"Comparison of ventilatory depression by carfentanil, fentanyl, and heroin, and reversal by opioid receptor antagonists in rats","authors":"Shawn M. Flynn ,&nbsp;Charles P. France","doi":"10.1016/j.neuropharm.2025.110601","DOIUrl":"10.1016/j.neuropharm.2025.110601","url":null,"abstract":"<div><div>Fentanyl and its analogs continue to drive the overdose crisis in the United States. It is unclear whether there are unique properties of fentanyls that increase the risk of opioid overdose compared with other opioid receptor agonists (e.g., heroin). This study compared the ventilatory depressant effects of the opioid receptor agonists heroin, fentanyl, and carfentanil, and reversal of those effects by opioid receptor antagonists. This study used whole-body plethysmography in rats to determine the ventilatory depressant effects of heroin (178–1780 μg/kg), fentanyl (5.6–56 μg/kg), and carfentanil (0.56–5.6 μg/kg) when administered alone and in mixtures, to compare the profile of effects across drugs and determine whether there are significant interactions between the drugs when co-administered. The potencies of the opioid receptor antagonists naloxone and diprenorphine to reverse opioid-induced ventilatory depression were compared across opioid agonists. All three agonists reduced minute volume with carfentanil being ∼50- and 100-fold more potent than fentanyl and heroin, respectively. The profile of effects on ventilation did not differ across agonists and no significant drug-drug interactions were detected. Naloxone and diprenorphine dose-dependently reversed the ventilatory depressant effects of each opioid agonist. Both antagonists were less potent at reversing the effects of carfentanil compared with reversing a functionally equivalent dose of heroin. These findings suggest that fentanyl might not produce unique effects on breathing that increase risk of overdose. That naloxone and diprenorphine were less potent to reverse the effects of carfentanil compared with an equivalent dose of heroin is consistent with existing literature and emphasizes the need for continued evaluation of potential differences in pharmacological properties across opioid receptor agonists.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"279 ","pages":"Article 110601"},"PeriodicalIF":4.6,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732436","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":"Ceftriaxone ameliorates tau phosphorylation and mislocalization in APP/PS1 AD mice by inhibiting endoplasmic reticulum stress","authors":"Niu-Niu Feng ,&nbsp;Li Li ,&nbsp;Li-Zhe Liu ,&nbsp;Ruo-Bing He ,&nbsp;Xiao-Hui Xian ,&nbsp;Li-Rong Liu ,&nbsp;Yu-Yan Hu ,&nbsp;Wen-Bin Li","doi":"10.1016/j.neuropharm.2025.110600","DOIUrl":"10.1016/j.neuropharm.2025.110600","url":null,"abstract":"<div><div>Tau phosphorylation and mislocalization are hallmark pathological features of Alzheimer's disease (AD), with endoplasmic reticulum stress (ERS) contributing to tauopathy. We previously showed that ceftriaxone (Cef) improves cognition in APP/PS1 AD mice through regulating GLT-1-mediated glutamate homeostasis. Here, we examined Cef's neuroprotection against ERS-related tauopathy. C57BL/6J and APP/PS1 AD mice were used. Cognitive functions were assessed by new object recognition (NOR), new location recognition (NLR) and Morris water maze (MWM) tests. Hippocampal synaptosomes were isolated using the Syn-PER™ Synaptic Protein Extraction Kit. Western blot analysis evaluates the protein levels of ERS markers, total and phosphorylated tau (Ser396/Ser262/Thr181), and Gsk3β. Transmission electron microscopy examined the endoplasmic reticulum ultrastructural changes of the hippocampus. Confocal 3D-reconstructed imaging assessed the phosphorylated tau (Ser396) distribution on the dendrites in the hippocampal region. The results showed that Cef treatment effectively reduced protein levels of ERS markers and restored endoplasmic reticulum ultrastructural integrity of hippocampus. Simultaneously, Cef treatment significantly alleviated tau phosphorylation levels, decreased accumulation of total and phosphorylated tau in synaptosomes, reduced phosphorylated tau (Ser396) distribution in dendritic compartments and inhibited Gsk3β activity in the hippocampus of APP/PS1 AD mice. Tunicamycin, a promoter of ERS, exacerbated cognitive impairments, tau phosphorylation levels and mislocalization, and Gsk3β activity, and notably, this exacerbation was inhibited by Cef treatment. Simultaneously, the ERS activation significantly inhibited Cef's above benefits on APP/PS1 AD mice. In conclusion, Cef improves cognitive impairment by alleviating ERS, decreasing Gsk3β activity, and reducing tau phosphorylation and mislocalization in the hippocampus of APP/PS1 AD mice.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"279 ","pages":"Article 110600"},"PeriodicalIF":4.6,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732435","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":"Neuropharmacology adenosine A2A receptor and glial glutamate transporter GLT-1 are synergistic targets to reduce brain hyperexcitability after traumatic brain injury in mice","authors":"Mariana Alves ,&nbsp;Rogério Gerbatin ,&nbsp;Rebecca Kalmeijer ,&nbsp;Denise Fedele ,&nbsp;Tobias Engel ,&nbsp;Detlev Boison","doi":"10.1016/j.neuropharm.2025.110599","DOIUrl":"10.1016/j.neuropharm.2025.110599","url":null,"abstract":"<div><div>Traumatic brain injury (TBI) is a leading cause of acquired epilepsy, with post-traumatic epilepsy (PTE) significantly contributing to morbidity and mortality. To date, there is no treatment capable to prevent the development of PTE, which remains an urgent unmet need. Previous studies suggest that adenosine A_2A receptor (A_2AR) activation and glutamate transporter 1 (GLT-1) dysregulation may contribute to epileptogenesis, however, it is unclear whether therapeutic targeting of the A_2AR or GLT-1 can attenuate TBI-induced hyperexcitability, and whether there are synergistic interactions between the two. Here, we investigated the therapeutic potential of two FDA approved drugs istradefylline (A_2AR inhibitor) and ceftriaxone (GLT-1 activator) in preventing long-lasting brain hyperexcitability in a clinically relevant rodent model of TBI. Adult male mice underwent controlled cortical impact (CCI)-induced TBI and were randomly assigned to istradefylline, ceftriaxone, istradefylline/ceftriaxone, or vehicle groups, receiving treatment during the first 24 h post-injury. Susceptibility to chemoconvulsant-evoked seizures was quantified at 4–5 weeks after CCI. We show that CCI caused a reduction in GLT-1 and an increase in A_2AR protein levels in the ipsilateral hippocampus. Transient acute treatment with istradefylline or ceftriaxone reduced brain hyperexcitability at 4–5 weeks post-TBI. Notably, mice treated with the combination of istradefylline and ceftriaxone exhibited increased GLT-1 levels, accompanied by further reductions in brain hyperexcitability, showing greater effects than either drug alone. Our findings identify a novel disease-modifying approach following TBI using a combination of two FDA-approved drugs which might be useful to mitigate the long-lasting brain hyperexcitability-induced by TBI.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"278 ","pages":"Article 110599"},"PeriodicalIF":4.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144702588","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":"Pantothenic acid-mediated inhibition of microglial inflammation via the JAK2/STAT3 pathway enhances motor function recovery after Spinal cord injury","authors":"Yuepeng Fang ,&nbsp;Ce Zhang ,&nbsp;Zhijie Yang ,&nbsp;Xiangrui Zhao ,&nbsp;yongcheng Yin ,&nbsp;zhengxin Jin ,&nbsp;Pengchong Zhu ,&nbsp;Bin Ning","doi":"10.1016/j.neuropharm.2025.110591","DOIUrl":"10.1016/j.neuropharm.2025.110591","url":null,"abstract":"<div><div>This study employed transcriptome sequencing and targeted metabolomics to delve into the molecular alterations in mouse spinal cords following spinal cord injury (SCI). Notably, a significant depletion of pantothenic acid (PA) was observed in the injured spinal cord, exhibiting an inverse correlation with microglial inflammation and activation. To further elucidate this relationship, experimental interventions using PA were conducted in SCI mouse models. The results demonstrated that PA administration effectively inhibited microglial inflammation via modulation of the JAK2/STAT3 signaling pathway. This inhibition not only mitigated the neuroinflammatory milieu but also fostered an environment conducive to axonal growth and neuronal regeneration. Consequently, SCI mice treated with PA exhibited improved motor function recovery compared to untreated controls. Our findings not only deepen the understanding of the relationship between PA and neuroinflammatory processes in SCI but also highlight the therapeutic potential of PA in promoting neuronal regeneration and functional recovery.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"278 ","pages":"Article 110591"},"PeriodicalIF":4.6,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699115","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":"Corticosterone modulates dopamine and serotonin1A receptor mediated regulation of prepulse inhibition and startle in male rats","authors":"Wendy K. Adams ,&nbsp;Maarten van den Buuse","doi":"10.1016/j.neuropharm.2025.110594","DOIUrl":"10.1016/j.neuropharm.2025.110594","url":null,"abstract":"<div><div>The aim of this project was to investigate the role of stress in neurotransmitter modulation of prepulse inhibition (PPI), a model of sensorimotor gating which is disrupted in schizophrenia and other illnesses. We studied the effect of adrenalectomy (ADX) and low and high levels of corticosterone (CORT) replacement on the effect of pharmacological modulators of PPI in rats. In ADX rats treated with a high dose of CORT (CORT200) the disruption of PPI caused by acute treatment with the dopamine receptor agonist, apomorphine, was significantly enhanced compared to ADX rats implanted with a control cholesterol pellet. On the other hand, CORT200 rats were less sensitive to the effect of the serotonin_1A receptor agonist, 8-OH-DPAT, while ADX rats implanted with a lower dose of CORT (CORT50) showed enhanced responding to this treatment. There were no differential effects on baseline PPI, or changes in startle or habituation of startle that could explain the effects on PPI. These data suggest that prolonged CORT treatment induces a major shift in dopaminergic and serotonergic mechanisms involved in the regulation of PPI. ADX and CORT replacement were found to have no effect on dopamine D₂ receptor densities in the nucleus accumbens (NAc), striatum or cingulate cortex, suggesting that our current observations are not due to changes in the levels of these receptors. These data may provide new insight into the role of stress in psychosis.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"278 ","pages":"Article 110594"},"PeriodicalIF":4.6,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144680359","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}