Neuropharmacology最新文献

{"title":"P2X7R-NF-κB-PDI signal pathway regulates LPS-induced impaired GSH synthesis by modulating ATF4-mediated xCT upregulation, S-nitrosylation of ASCT2 and GSHS expressions in the mouse hippocampus","authors":"Ji-Eun Kim ,&nbsp;Su Hyeon Wang ,&nbsp;Duk-Shin Lee","doi":"10.1016/j.neuropharm.2025.110696","DOIUrl":"10.1016/j.neuropharm.2025.110696","url":null,"abstract":"<div><div>Protein disulfide isomerase (PDI) augments lipopolysaccharide (LPS)-induced nuclear factor-κB (NF-κB) activation by integrating Toll-like receptor 4 (TLR4) and P2X7 receptor (P2X7R) signaling pathways in a positive feedback manner. However, it has been largely unknown whether PDI is involved in altered glutathione (GSH) biosynthesis, which is mediated by P2X7R, in response to LPS. In the present study, LPS-induced NF-κB activation increased PDI expression, but decreased solute carrier 1 A5 (ASCT2) level in the <em>P2X7</em>^<em>+/+</em> mouse hippocampus. <em>PDI</em> knockdown attenuated ASCT2 downregulation and <em>S</em>-nitrosylated (SNO-) ASCT2 level in response to LPS. This LPS-induced NF-κB-PDI activation also increased <em>activating transcription factor 4 (</em>ATF4) expression in astrocytes, which elicited cystine:glutamate transporter (xCT) upregulation, but decreased ASCT2 and GSH synthetase (GSHS) expression. Furthermore, <em>S</em>-nitrosylation of PDI modulated ATF4-mediated xCT upregulation in response to LPS. SN50 (a NF-κB inhibitor), <em>PDI</em> knockdown and <em>ATF4</em> siRNA mitigated the decreased GSH content induced by LPS. Under physiological condition, <em>P2X7R</em> deletion did not affect basal PDI, ATF4, xCT and SNO-ASCT2 levels. However, it increased ASCT2 expression and decreased SNO-PDI level. <em>P2X7R</em> ablation ameliorated (1) PDI, ATF4 and xCT2 upregulations, (2) <em>S</em>-nitrosylation of ASCT2 and PDI and (3) ASCT2 downregulation in response to LPS. These findings indicate that P2X7R-NF-κB-PDI signal pathway may inhibit GSH biosynthesis in response to LPS by modulating expression/<em>S</em>-nitrosylation of ASCT2 and ATF4-mediated xCT regulation in response to LPS.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"281 ","pages":"Article 110696"},"PeriodicalIF":4.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091998","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":"Xanomeline treatment attenuates cocaine self-administration in rats and nonhuman primates","authors":"Samuel A. Marsh ,&nbsp;Nicholas Heslep ,&nbsp;Carol A. Paronis ,&nbsp;Jack Bergman ,&nbsp;S. Stevens Negus ,&nbsp;Matthew L. Banks","doi":"10.1016/j.neuropharm.2025.110686","DOIUrl":"10.1016/j.neuropharm.2025.110686","url":null,"abstract":"<div><div>The lack of an FDA-approved pharmacotherapy to combat cocaine use disorder (CUD) is an ongoing and urgent public health challenge. Emerging evidence suggests that the muscarinic acetylcholine system modulates mesolimbic dopamine release and thus may serve as a suitable target for novel CUD medications. The M1/M4-preferring muscarinic agonist xanomeline was recently approved by the Food and Drug Administration for schizophrenia management, and a previous study in male rats suggested that xanomeline treatment attenuated cocaine self-administration in a cocaine-vs-food choice procedure. The present study was conducted to further examine xanomeline treatment effectiveness on cocaine self-administration in male and female rats and nonhuman primates. Both male and female rats and monkeys were trained to self-administer cocaine during daily behavioral sessions. Repeated xanomeline treatment significantly decreased cocaine choice in rats similar to both pharmacological (amphetamine maintenance) and non-pharmacological (increasing alternative reinforcer value) positive controls. In separate groups of monkeys, acute xanomeline pretreatment decreased cocaine-vs-food choice in three out of four monkeys and selectively decreased cocaine-, but not food-maintained responding, under a multiple schedule of cocaine and food reinforcement in three out of four monkeys. Overall, the consistent effectiveness of xanomeline to reduce IV cocaine self-administration in both rodents and nonhuman primate supports its further evaluation as a CUD medication in humans.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"281 ","pages":"Article 110686"},"PeriodicalIF":4.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086641","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":"Neuronal ensembles formed rapidly in the prelimbic cortex mediate initial and maintained cocaine-seeking behavior in male and female rats","authors":"Bo W. Sortman ,&nbsp;Samantha Rakela ,&nbsp;Berk Cerci ,&nbsp;Sarah Paprotna ,&nbsp;Jordan Harrow ,&nbsp;Sophie Hao ,&nbsp;Michel van den Oever ,&nbsp;Brandon L. Warren","doi":"10.1016/j.neuropharm.2025.110684","DOIUrl":"10.1016/j.neuropharm.2025.110684","url":null,"abstract":"<div><div>Substance use disorder is a complex neurobiological disease thought to be partially driven by aberrant forms of learning and memory. The cellular basis of memory is hypothesized to be small subsets of interconnected networks formed during the acquisition of behavior called neuronal ensembles. We interrogate neuronal ensembles by utilizing a dual viral approach that expresses Cre^ERT2 under the control of the c-Fos promoter in conjunction with a Cre-dependent inhibitory DREADD. This approach gives us the temporal specificity to target neuronal ensembles formed during the acquisition of cocaine seeking in the prelimbic cortex. First, we demonstrate that neuronal ensembles in the prelimbic cortex are rapidly recruited and mediate cocaine seeking. Second, we show that the neuronal ensembles formed during behavioral acquisition are an enduring population that continues to be behaviorally relevant once rats are well-trained. Finally, through the combination of retrograde tract tracing and Fos immunohistochemistry, we show that neuronal ensembles in the prelimbic cortex recruit the nucleus accumbens core and shell after behavioral acquisition of cocaine self-administration. Collectively, we show that the prelimbic neuronal ensembles that mediate cocaine seeking are highly specific to context and behavioral conditions and recruit downstream projection targets post-acquisition.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"281 ","pages":"Article 110684"},"PeriodicalIF":4.6,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080496","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":"Intranasal AdipoRon improves motor function in a rat model of Parkinson's disease by promoting neurogenesis in the nigrostriatal pathway","authors":"Seyed Zanyar Athari ,&nbsp;Fereshteh Farajdokht ,&nbsp;Mohammad Karimipour ,&nbsp;Mohammad Reza Alipour ,&nbsp;Gisou Mohaddes","doi":"10.1016/j.neuropharm.2025.110687","DOIUrl":"10.1016/j.neuropharm.2025.110687","url":null,"abstract":"<div><div>Parkinson's disease (PD) is a neurodegenerative disorder characterized by drastically reduced synaptic plasticity and neurogenesis, possibly due to abnormal α-synuclein deposition. Boosting endogenous neurogenesis is a potential strategy for halting cell death and restoring brain function. AdipoRon (AR) has been shown to promote progenitor cell proliferation and differentiation in neurological disorders. This study investigated the effect of intranasal (IN) AR on neurogenesis in the nigrostriatal pathway and motor function in a rat PD model. Dopaminergic neuronal degeneration was induced by administering 6-hydroxydopamine (6-OHDA) into the left medial forebrain bundle. One week post-PD induction, hemiparkinsonian rats received either levodopa (10 mg/kg, gavage) or AR (0.1, 1, and 10 μg/rat, IN) for 21 days. To evaluate adult neurogenesis, 5-bromodeoxyuridine (BrdU) was injected for 5 days at the start of treatments. Motor functions were assessed 5 weeks post-6-OHDA injection, and the animals were sacrificed for analysis. The number of BrdU and NeuN/BrdU positive cells in the ipsilateral substantia nigra (SN) was determined. Moreover, the density of tyrosine hydroxylase (TH)-positive fibers and the level of cerebral dopamine neurotrophic factor (CDNF), Zif-268, and synaptophysin (SYP) proteins were examined in the striatum. Our findings indicated that AR dose-dependently restored motor function and increased striatal CDNF, SYP, and Zif-268 protein expression in 6-OHDA-lesioned rats. Besides, AR 10 μg enhanced the number of NeuN + cells in the SN and dopaminergic fiber density (TH + terminals) in the striatum. These findings indicated that AR improved motor symptoms by promoting neurogenesis and synaptic transmission in the nigrostriatal pathway in PD rats.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"281 ","pages":"Article 110687"},"PeriodicalIF":4.6,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080354","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 “Chronic psilocybin administration increases sociability and alters the gut microbiome in male wild-type mice but not in a preclinical model of obsessive-compulsive disorder” [Neuropharmacology 279 (2025) 110648]","authors":"James J. Gattuso ,&nbsp;Geraldine Kong ,&nbsp;Bilgenur Bezcioglu ,&nbsp;Da Lu ,&nbsp;Millicent N. Ekwudo ,&nbsp;Carey Wilson ,&nbsp;Carolina Gubert ,&nbsp;Anthony J. Hannan ,&nbsp;Thibault Renoir","doi":"10.1016/j.neuropharm.2025.110679","DOIUrl":"10.1016/j.neuropharm.2025.110679","url":null,"abstract":"","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"280 ","pages":"Article 110679"},"PeriodicalIF":4.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145054867","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":"Ionic and signaling mechanisms involved in the excitation of entorhinal neurons by group I mGluRs","authors":"Saobo Lei,&nbsp;Chidiebele S. Oraegbuna,&nbsp;Cody A. Boyle,&nbsp;Morgan R. Mastrud","doi":"10.1016/j.neuropharm.2025.110683","DOIUrl":"10.1016/j.neuropharm.2025.110683","url":null,"abstract":"<div><div>Activation of metabotropic glutamate receptors (mGluRs) modulates neuronal excitability, synaptic transmission and plasticity in the brain. While group I mGluRs in layer III pyramidal neurons in the entorhinal cortex (EC) are implicated in persistent firing which is considered as a cellular mechanism for working memory, the underlying ionic and signaling mechanisms have not been determined. Here, we showed that application of (S)-3,5-dihydroxyphenylglycine (DHPG), the selective agonist for group I mGluRs, excited layer III pyramidal neurons of the EC via activation of both mGluR1 and mGluR5. DHPG excited layer III pyramidal neurons by activating TRPC5 channels and depressing GIRK type of inwardly rectifying K⁺ (Kir) channels. The functions of G proteins, phospholipase Cβ (PLCβ) and PLCβ-mediated depletion of PIP₂ were required for group I mGluR-mediated activation of TRPC5 and depression of GIRK channels, whereas intracellular Ca²⁺ release and PKC were not involved in DHPG-elicited excitation of layer III pyramidal neurons. We also found that diacylglycerol was involved in DHPG-elicited activation of TRPC5 channels. Our results may serve as a signaling and ionic mechanism to explain the physiological functions of group I mGluRs <em>in vivo</em>.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"280 ","pages":"Article 110683"},"PeriodicalIF":4.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057391","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":"Adolescent intermittent ethanol exposure produces sex-specific development of functional tolerance to ethanol-induced motor impairment and hypothermia","authors":"Sarah Trapp,&nbsp;Andrew S. Vore,&nbsp;Ashley Lutzke,&nbsp;Elena I. Varlinskaya,&nbsp;Terrence Deak","doi":"10.1016/j.neuropharm.2025.110682","DOIUrl":"10.1016/j.neuropharm.2025.110682","url":null,"abstract":"<div><div>Adolescent intermittent ethanol (AIE) exposure has been shown to attenuate sensitivity to ethanol effects, suggesting tolerance development. The present studies sought to determine whether AIE-exposed male and female rats would develop tolerance to ethanol-induced motor impairment and hypothermia, and to test the effects of AIE on ethanol-metabolizing enzymes in the brain. Adult rats showed motor impairment at 2 g/kg i.p. ethanol, with intoxicated practice attenuating ethanol-induced motor impairment (Experiments 1 &amp; 2). AIE-exposed males, but not females, showed reduced motor impairment when challenged with 2 g/kg i.p. ethanol 1 day after AIE, suggesting tolerance development (Experiment 3). AIE-exposed males, but not females, became tolerant to ethanol-induced hypothermia during AIE (Experiment 4). Brain and/or blood ethanol levels were not affected by AIE. No tolerance was evident 30 days later. Gene expression of ethanol-metabolizing enzymes was assessed in animals with a history of AIE and challenged with 2.5 g/kg i.p. ethanol in adulthood (Experiment 5). In females, AIE reduced catalase (CAT) and aldehyde dehydrogenase 2 (ALDH2) expression in the amygdala. Males showed increased alcohol dehydrogenase 1 (ADH1) expression in the amygdala following an ethanol challenge. Experiment 6 revealed transient effects of AIE on cell-type-specific expression of ADH1 and ALDH2. One day after AIE, AIE-exposed males showed a reduction in ADH1 colocalized with neurons in the cerebellum, whereas AIE-exposed females showed a reduction in ALDH2, particularly in microglia, in the hippocampus. Together, these findings revealed sex-specific, short-term tolerance to ethanol-induced motor impairment and hypothermia during AIE that was independent of ethanol pharmacokinetics.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"280 ","pages":"Article 110682"},"PeriodicalIF":4.6,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040872","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":"Contraceptive hormone ethinyl estradiol but not levonorgestrel modulates the role of reinforcer-enhancement in nicotine self-administration in ovary-intact female Sprague-Dawley rats","authors":"Kathleen R. McNealy ,&nbsp;MacKenzie L. Knabel ,&nbsp;Scott T. Barrett ,&nbsp;Cassandra D. Gipson ,&nbsp;Tierney K. Lorenz ,&nbsp;Rick A. Bevins","doi":"10.1016/j.neuropharm.2025.110681","DOIUrl":"10.1016/j.neuropharm.2025.110681","url":null,"abstract":"<div><div>Hormonal contraceptives containing a synthetic estrogen (e.g., ethinyl estradiol/EE) and/or a progestin (e.g., levonorgestrel/LEVO) are associated with heightened nicotine use. Whether altered intake reflects changes in nicotine reinforcement or nicotine enhancement of co-occurring reinforcers is unknown. Reinforcer-enhancement is evidenced when nicotine self-administration increases when delivered with a reinforcing visual stimulus (VS). We examined EE and LEVO effects on nicotine reinforcement and reinforcer-enhancement in ovary-intact female Sprague-Dawley rats. Rats were implanted with a jugular catheter and received daily EE (Vehicle, 0.125 [Low], or 0.18 [High] μg/day; Experiment 1 N = 95) or LEVO (Vehicle, 0.3 [Low], or 0.6 [High] μg/day; Experiment 2 N = 113) injections. Rats responded for saline, 0.03 or 0.06 mg/kg/inf nicotine during two phases: the Infusion Only phase, responding only for their assigned solution, and the Infusion + VS phase, responding for their assigned solution and a VS. Each phase consisted of two Fixed Ratio-1 and ten Variable Ratio-3 sessions. The Infusion + VS phase included five additional Progressive Ratio sessions. In both experiments, only 0.06 mg/kg/inf nicotine maintained self-administration during the Infusion Only phase. This self-administration was unchanged by EE or LEVO. Nicotine self-administration increased during the Infusion + VS phase. In Experiment 1, 0.03 mg/kg/inf nicotine self-administration decreased with increasing EE dose; 0.06 mg/kg/inf nicotine self-administration was unchanged. For Experiment 2, LEVO did not alter self-administration. EE and LEVO were physiologically effective, evidenced by disrupted estrous cycling and EE increasing uterine weights. EE but not LEVO altered nicotine reinforcer-enhancement. These findings suggest a potential behavioral mechanism by which hormonal contraceptives alter nicotine intake in women.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"280 ","pages":"Article 110681"},"PeriodicalIF":4.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033657","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":"Progesterone attenuates the effects of cocaine on hypermobility and dopaminergic transmission in the nucleus accumbens","authors":"William N. Sánchez ,&nbsp;José A. Pochapski ,&nbsp;A. Leslie Morrow ,&nbsp;Roberto Andreatini ,&nbsp;Donita L. Robinson ,&nbsp;Rainer K.W. Schwarting ,&nbsp;Sergi Ferré ,&nbsp;Claudio Da Cunha","doi":"10.1016/j.neuropharm.2025.110680","DOIUrl":"10.1016/j.neuropharm.2025.110680","url":null,"abstract":"<div><div>Currently there is no pharmacological treatment for cocaine use disorder. Previous studies have shown that progesterone can mitigate the behavioral effects induced by cocaine in both animal models and humans. However, the underlying mechanisms through which progesterone exerts this effect remain poorly understood. While it was already known that exogenous progesterone can decrease dopamine release in the nucleus accumbens (NAc) of male rats, it remains unclear whether progesterone could also reduce the cocaine-induced increase in extracellular dopamine levels. Here we evaluated if exogenous progesterone could reduce cocaine-induced increases in mobility, locomotion, ultrasonic vocalizations and electrically-evoked change in dopamine levels in the NAc of adult male and female rats. Progesterone decreased electrically-evoked dopamine levels, locomotion and mobility in both males and females, being more effective in female rats. Moreover, progesterone attenuated the cocaine-induced increase in the electrically-evoked dopamine concentration in the NAc. Rats exhibited stimulant euphoric-like and rewarding effects of cocaine through increased mobility, locomotion, and 50-kHz ultrasonic vocalization (USV) calls. We also found that progesterone attenuates these effects of cocaine in female, but not male, rats, suggesting that progesterone may dampen the rewarding, euphoric, and psychostimulant effects of cocaine, but with sex differences.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"280 ","pages":"Article 110680"},"PeriodicalIF":4.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019429","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":"Repetitive stress decreases norepinephrine's dynamic range in the auditory cortex","authors":"Ekaterina Kaganovski ,&nbsp;Jennifer Resnik","doi":"10.1016/j.neuropharm.2025.110676","DOIUrl":"10.1016/j.neuropharm.2025.110676","url":null,"abstract":"<div><div>Norepinephrine (NE) is a key neuromodulator in the brain with a wide range of functions. It regulates arousal, attention, and the brain's response to stress, enhancing alertness and prioritizing relevant stimuli. In the auditory domain, NE modulates neural processing and plasticity in the auditory cortex by adjusting excitatory-inhibitory balance, tuning curves, and signal-to-noise ratio. However, stress adds a layer of complexity to NE's cortical influence. Although acute stress can transiently boost locus coeruleus's activity and NE release, the effect of repeated stress on NE dynamics in the auditory cortex remains unclear. Using chronic two-photon imaging of the genetically encoded NE sensor GRAB_NE1m in head-fixed mice, we show that repetitive stress strongly attenuates NE responses to high-intensity sounds in the auditory cortex, with continued decline as the stressor becomes chronic. Additionally, repetitive stress disrupts normal habituation within each session: mice no longer exhibit the typical decrease in NE activation following repeated presentations of a loud stimulus. Our findings demonstrate that repetitive stress narrows the dynamic range and adaptability of the noradrenergic system in the auditory cortex, markedly reducing NE responses to intense sounds and eliminating the expected within-session habituation. By demonstrating that prolonged stress compromises NE dynamics in the auditory cortex, our results provide mechanistic insights into how repetitive stress could degrade auditory processing and potentially exacerbate hypervigilance or anxiety-like states.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"280 ","pages":"Article 110676"},"PeriodicalIF":4.6,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023823","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}