Neuropharmacology最新文献

{"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":"Ginsenoside Re exerts neuroprotective in MPTP mice: potential links to gut microbiota and serum metabolism","authors":"Jie Li ,&nbsp;Guijia Zhao ,&nbsp;Chunhui Yu ,&nbsp;Yi Qu ,&nbsp;Xiaorui Shen ,&nbsp;Yuting Zhao ,&nbsp;Jinnan Zhang ,&nbsp;Wenhui Lian ,&nbsp;Yu Zhao","doi":"10.1016/j.neuropharm.2025.110596","DOIUrl":"10.1016/j.neuropharm.2025.110596","url":null,"abstract":"<div><div>A Parkinson's disease (PD) model was established using male C57BL/6 mice administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), through which the neuroprotective effect of Ginsenoside Re (G-Re) was investigated. Although G-Re has demonstrated beneficial effects in MPTP-treated mice, its <em>in vivo</em> activity and the mechanisms underlying its therapeutic potential in PD remain insufficiently understood. In this study, microbiomics and metabolomics analyses were comprehensively employed to investigate gut microbial and metabolic changes in MPTP-induced mice following G-Re intervention, with the aim of elucidating G-Re's mechanisms of action in PD. G-Re administration was found to alleviate dyskinesia, attenuate dopaminergic neuronal loss, reduce alpha-synuclein aggregation, and enhance antioxidant defenses in MPTP-treated mice. Notably, G-Re significantly increased the relative abundance of <em>Bifidobacterium</em>, <em>Clostridium</em>, and <em>Prevotella</em> while decreasing the relative abundance of <em>Akkermansia</em>, <em>Sutterella</em>, and <em>Allobaculum</em>, thereby contributing to the restoration of gut microbiota composition. Non-targeted metabolomics revealed that G-Re exerted neuroprotective effects by modulating disruptions in the arachidonic acid, sphingolipid, and linoleic acid metabolic pathways, as well as pathways related to the biosynthesis of unsaturated fatty acids. Correlation analyses further demonstrated a significant association between specific gut microbes and the sphingolipid metabolic pathway. In addition, G-Re was found to inhibit pro-apoptotic proteins such as Bax and caspase-3 within the sphingolipid pathway while promoting the activity of anti-apoptotic proteins. Collectively, these findings provide both a scientific and theoretical basis supporting the therapeutic potential of G-Re in the treatment of PD.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"282 ","pages":"Article 110596"},"PeriodicalIF":4.6,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732437","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":"The mitochondria-targeted hydrogen sulfide donor AP39 reduces cortical stroke volume and improves motor function in a photothrombotic stroke model in mice in a sex-dependent manner","authors":"Jakub Jurczyk ,&nbsp;Zuzanna Guzda ,&nbsp;Alicja Skórkowska ,&nbsp;Żaneta Broniowska ,&nbsp;Małgorzata Piechaczek ,&nbsp;Aleksandra Więcek ,&nbsp;Emilia Schulze ,&nbsp;Angelika Ziaja ,&nbsp;Roberta Torregrossa ,&nbsp;Matthew Whiteman ,&nbsp;Michel Soares Mesquita ,&nbsp;Bartosz Pomierny ,&nbsp;Lucyna Pomierny-Chamioło","doi":"10.1016/j.neuropharm.2025.110602","DOIUrl":"10.1016/j.neuropharm.2025.110602","url":null,"abstract":"<div><div>Despite many years of research, the treatment for patients affected by ischemic stroke remains very limited and insufficient. Currently, new neuroprotective treatment strategies are being sought to reduce brain tissue damage in the penumbra zone. One of these strategies involves the use of a hydrogen sulfide donor, the compound AP39, which mitochondria-targeted and, in very low concentrations, has shown a favorable action profile in preclinical studies across various disease models.</div><div>In this study, we evaluated whether the administration of AP39, given 10 min after photothrombotic focal cerebral stroke, affects motor performance in a skilled reaching task in both female and male mice. We also assessed cerebral blood flow using laser speckle contrast analysis, stroke volume via MRI at 24 h, 3 days, and 6 days post-stroke, as well as the expression of mitochondrial proteins TOMM20, COX4, PINK1 and Parkin as markers of mitophagy in cells.</div><div>Our results showed significant improvement in motor function, increased blood flow and noticeably lower stroke volume, and TOMM20 and COX4 expression with concomitant upregulation of PINK1 and Parkin expression at day 6 in men treated with AP39 after focal cortical stroke. In females, the beneficial effect was limited, with only a slight reduction in stroke volume observed, without any impact on skilled task performance. These results indicate that AP39 has neuroprotective potential, but it is sex dependent.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"279 ","pages":"Article 110602"},"PeriodicalIF":4.6,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144722072","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":"Subchronic amphetamine decreases hyperactivity, anti-social behaviour and anhedonia in dopamine transporter knockout rats: role of prefrontal glutamate","authors":"Mina Sadighi ,&nbsp;Kyriaki Foka ,&nbsp;Francesca Mottarlini ,&nbsp;Ellen Burg ,&nbsp;Sofia Taddini ,&nbsp;Damiana Leo ,&nbsp;Fabrizio Sanna ,&nbsp;Lucia Caffino ,&nbsp;Fabio Fumagalli ,&nbsp;Judith R. Homberg","doi":"10.1016/j.neuropharm.2025.110597","DOIUrl":"10.1016/j.neuropharm.2025.110597","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Hyperdopaminergia is a key feature of neuropsychiatric disorders including schizophrenia, attention deficit hyperactivity disorder, and bipolar disorder and can be modeled using dopamine transporter knockout (DAT KO) rats. Previous studies have shown that acute amphetamine has a paradoxical calming effect in DAT KO rats, but the effects of repeated amphetamine treatment are unknown.</div></div><div><h3>Experimental approach</h3><div>We studied the effect of subchronic amphetamine on hyperdopaminergia-related disease symptoms and underlying mechanisms using male and female DAT KO rats. We measured locomotor activity, anxiety-like behaviour, social behaviour, anhedonia and problem-solving behaviour at baseline and after 10 days of amphetamine treatment and assessed protein expression changes in the glutamate system in the prefrontal cortex.</div></div><div><h3>Key results</h3><div>Both female and male DAT KO rats exhibited hyperlocomotion compared to control rats. Subchronic amphetamine treatment significantly dampened this effect in female, but not in male DAT KO rats. Additionally, amphetamine increased sociability in female, but not in male DAT KO rats. From a molecular point of view, we observed differences in the modulation of glutamatergic transmission between males and females mainly at the level of the infralimbic, but not prelimbic, prefrontal cortex, suggesting that the glutamatergic synapse may contribute to the behavioral response to amphetamine between the two sexes.</div></div><div><h3>Conclusion and implications</h3><div>Subchronic amphetamine treatment decreased the hyperactivity, anxiety-like, anti-social and anhedonic phenotypes of female DAT KO rats, potentially by modulating glutamate transmission in the prefrontal cortex. These findings foster further research into the treatment of hyperdopaminergia-related disorders.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"279 ","pages":"Article 110597"},"PeriodicalIF":4.6,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144712994","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":"Sex-dependent role of Neuropeptide-S on anxiety, fear conditioning, and alcohol seeking in alcohol preferring rats","authors":"Min Li ,&nbsp;Sara De Carlo ,&nbsp;Laura Soverchia ,&nbsp;Scott P. Runyon ,&nbsp;Stewart Clark ,&nbsp;Marisa Roberto ,&nbsp;Carolina L. Haass-Koffler ,&nbsp;Roberto Ciccocioppo ,&nbsp;Douglas J. Sheffler ,&nbsp;Nazzareno Cannella","doi":"10.1016/j.neuropharm.2025.110598","DOIUrl":"10.1016/j.neuropharm.2025.110598","url":null,"abstract":"<div><div>Alcohol Use Disorder (AUD) is a global health concern, with stress playing a crucial role in its development and persistence. Currently, no pharmacotherapies specifically targeting stress are approved for AUD treatment. Neuropeptide S (NPS) plays a dual role in stress regulation, exhibiting both anxiolytic and stress-enhancing effects. While NPS reduces alcohol self-administration (ASA) in alcohol preferring rats, its role in AUD-related stress and anxiety remains unclear.</div><div>This study investigated the behavioral effects of NPS in male and female Marchigian Sardinian alcohol-preferring (msP) rats. To assess its impact on locomotion, anxiety, and fear memory, we conducted an open-field, an elevated plus maze (EPM), and a fear conditioning (FC) paradigm following intracerebroventricular administration of NPS. Furthermore, we examined the effects of NPS on ASA and yohimbine-induced reinstatement of alcohol-seeking in msP rats.</div><div>Our results indicate that NPS administration increased locomotor activity in both sexes and selectively alleviated generalized anxiety levels in male rats in the EPM test. In the FC task, administration of NPS immediately after FC test facilitated the extinction of fear memories in females but not in males. Notably, NPS reduced ASA in both female and male rats but did not alter yohimbine-induced reinstatement of alcohol-seeking. In conclusion, NPS modulates anxiety in a sex-dependent manner. Since both alcohol and NPS alleviate anxiety and fear conditioning in msP rats, NPS may reduce alcohol intake by replacing the anxiolytic properties of alcohol. These effects appear to be sex-dependent, with NPS primarily alleviating generalized anxiety in males and facilitating fear extinction in females.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"278 ","pages":"Article 110598"},"PeriodicalIF":4.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695328","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}