Psychopharmacology最新文献

{"title":"Behavioral economic demand for ethanol in Long Evans rats: Influence of choice context, sex, and vapor history.","authors":"Olivia A Colarusso, Jeffrey L Weiner","doi":"10.1007/s00213-026-07168-8","DOIUrl":"10.1007/s00213-026-07168-8","url":null,"abstract":"<p><strong>Rationale: </strong>Behavioral economic demand analyses are widely used in human studies to quantify the motivational value of ethanol. However, the extent to which ethanol demand is modulated by alternative reinforcer availability and by biological factors, such as sex and history of ethanol vapor exposure, remains unstudied in preclinical animal models.</p><p><strong>Objectives: </strong>This study used a novel rodent operant paradigm to examine how choice context, sex, and ethanol vapor exposure history influence both demand for ethanol and absolute intake.</p><p><strong>Methods: </strong>Male and female Long Evans rats with or without a history of binge-like ethanol vapor exposure completed self-administration sessions under choice (sweetened ethanol and sucrose) and no-choice (sweetened ethanol only) conditions. Ethanol fixed-ratio (FR) increased across sessions to generate demand curves while sucrose remained under a FR5, when available. Cost-dependent changes in seeking behavior (demand curves) and absolute intake (g/kg) were evaluated using complementary analytical approaches.</p><p><strong>Results: </strong>Increasing ethanol FR suppressed ethanol intake across all conditions. Vapor-exposed rats, who previously demonstrated reduced ethanol-directed choice behavior, demonstrated heightened sensitivity to ethanol price specifically when an alternative reinforcer was available. This context-dependent effect was absent under no-choice conditions. Notably, demand elasticity did not differ by sex, yet sex differences in absolute ethanol intake emerged, suggesting dissociable mechanisms. Substitution analyses revealed substantial individual heterogeneity.</p><p><strong>Conclusions: </strong>These findings highlight the interaction between environmental and biological factors in shaping ethanol valuation, further characterizing self-administration as a dynamic process. Additionally, these results highlight the importance of measuring seeking and consummatory behaviors alongside achieved dose (g/kg) in oral self-administration paradigms.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting α5-GABAA receptors to restore dopamine system function in a translationally relevant model of perimenopausal psychosis.","authors":"Kayla Lilly, Dishary Sharmin, James M Cook, Daniel J Lodge, Stephanie M Perez","doi":"10.1007/s00213-026-07171-z","DOIUrl":"https://doi.org/10.1007/s00213-026-07171-z","url":null,"abstract":"<p><strong>Background: </strong>Perimenopause marks a high-risk period for psychiatric instability, often precipitating or exacerbating disorders like schizophrenia. While traditional antipsychotics can be effective, they often worsen vasomotor symptoms and carry side effects that drive high discontinuation rates. We hypothesized that hippocampal hyperactivity, resulting from a decrease in GABAergic transmission, drives mesolimbic dopamine dysregulation in this state. Thus, we proposed that this circuit-level dysfunction can be reversed by targeting α5-containing GABA_A receptors (α5-GABA_AR).</p><p><strong>Methods: </strong>We used the translationally relevant 4-vinylcyclohexene diepoxide (VCD) model of perimenopause, which mimics the progressive loss of ovarian follicles and hormonal instability seen in women. We assessed α5-GABA_AR expression in the ventral hippocampus (vHipp) and utilized in vivo extracellular electrophysiology to record ventral tegmental area (VTA) dopamine neuron activity following systemic administration of the selective α5-GABA_AR positive allosteric modulator (PAM), MP-III-022.</p><p><strong>Results: </strong>VCD-treated rats exhibited significantly elevated dopamine neuron population activity. This aberrant dopamine activity was completely reversed by systemic administration of MP-III-022.</p><p><strong>Conclusions: </strong>These findings offer a pharmacologically distinct alternative to standard D2 receptor-targeted antipsychotics. Thus, modulating hippocampal-driven dopamine dysregulation via α5-GABA_AR represents an efficacious and translatable strategy for treating perimenopausal psychiatric symptoms with the potential for significantly improved patient tolerability.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149031318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulatory effects of α7-nicotinic cholinergic receptors on perceptual sensitivity in a visual signal detection task.","authors":"Harry J Robson, Alexander R H Matthews, Livia J F Wilod Versprille, Johann du Hoffmann, Jeffrey W Dalley","doi":"10.1007/s00213-026-07169-7","DOIUrl":"https://doi.org/10.1007/s00213-026-07169-7","url":null,"abstract":"<p><strong>Rationale: </strong>Cholinergic signalling is critical for attentional control and signal detection, yet the contribution of specific acetylcholine receptor (AChR) subtypes remains poorly understood. Although the α7 nicotinic AChR (nAChR) holds promise as a target for cognition-enhancing therapy, clinical findings to date have been inconsistent.</p><p><strong>Objective: </strong>To investigate the effects of putative cognitive enhancing drugs, including those targeting cholinergic transmission and α7 nAChRs on a visual signal detection task (SDT).</p><p><strong>Methods: </strong>Male and female Sprague Dawley rats were trained on an SDT. Cholinergic transmission was probed systemically with nicotinic and muscarinic receptor antagonists (mecamylamine and scopolamine), a cholinesterase inhibitor (galantamine), an M4-AChR positive allosteric modulator (PAM; VU0467154), an α7 nAChR antagonist (MLA), an α7 nAChR PAM (CCMI), and an α7 nAChR partial agonist (SSR-180,711). Catecholaminergic transmission was probed using the catechol-O-methyltransferase (COMT) inhibitor tolcapone. A novel, trial-level signal detection theory-based generalised linear mixed-effects model (SDT-GLMM) was used to index response bias and perceptual sensitivity (d'), the latter reflecting subjects' ability to discriminate signal from noise.</p><p><strong>Results: </strong>High dose mecamylamine impaired d' and hit rate and slowed responding. Galantamine significantly improved d' at moderate doses but not when a distractor was present. MLA produced dose-dependent improvements in d' that were preserved under distraction. In contrast, positive allosteric modulation and activation of α7 nAChRs impaired task performance. Scopolamine produced marked behavioural slowing, whereas VU0467154 and tolcapone did not reliably affect d'.</p><p><strong>Conclusions: </strong>These findings demonstrate that α7 nAChR modulation bidirectionally and dose-dependently regulates perceptual sensitivity, irrespective of attentional distraction. These findings have implications for targeted cognitive enhancement in disorders of attention.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential contributions of striatal dopaminergic pathways to visuomotor conditional learning.","authors":"Oren Princz-Lebel, Meira M F Machado, Miguel Skirzewski, Harleen Rai, Samina Panjwani, Anthony Chu, Claire A Lemieux, Daniel Palmer, Neeki Derhami, Vania F Prado, Marco A M Prado, Lisa M Saksida, Timothy Bussey","doi":"10.1007/s00213-026-07165-x","DOIUrl":"https://doi.org/10.1007/s00213-026-07165-x","url":null,"abstract":"<p><strong>Rationale: </strong>Midbrain dopamine (DA) neurons project principally towards the striatum, serving as key regulators of movement, motivation, and cognition. Different striatal dopaminergic (DA) pathways may regulate different aspects of cognition.</p><p><strong>Objectives: </strong>We investigated how different striatal DA pathways contribute to a known function of the striatum, visuomotor conditional learning.</p><p><strong>Methods: </strong>Using fiber photometry, we recorded DA transients in these regions as mice learned the touchscreen Visuo-Motor Conditional Learning task.</p><p><strong>Results: </strong>DA transients in all regions dynamically tracked task events, but differed in the timing of peak responses and ramp-like activity preceding a choice, indicating region-specific temporal dynamics across learning. Manipulations of reward probability revealed DA transients in all regions during reward delivery and omission that are consistent with an interpretation in terms of reward prediction error. Thus, DA dynamics in all regions could indicate involvement in visuomotor conditional learning. Therefore, to determine whether nigrostriatal or mesolimbic DA is necessary for learning, we chemogenetically inhibited DA striatal afferents, revealing that only DLS-projecting nigrostriatal DA, and not NAc-projecting mesolimbic striatal DA, was necessary for learning the task.</p><p><strong>Conclusion: </strong>These findings demonstrate functional heterogeneity of aspects of striatal DA signaling, and selective causal roles in the learning of visuomotor conditional learning.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resetting the hippocampal buffer: a neurocognitive account of psychedelic therapy for anxiety-related psychopathology.","authors":"Hugh McGovern, Nick Wellman, Brendan Hutchinson, Lena Oestreich, Samuel Cooper, Gregory A Fonzo, Manoj K Doss","doi":"10.1007/s00213-026-07163-z","DOIUrl":"https://doi.org/10.1007/s00213-026-07163-z","url":null,"abstract":"<p><p>Psychedelics (hallucinogenic 5-HT_2A agonists such as psilocybin) are being investigated for their potential to treat a range of conditions, including anxiety-related psychopathology. Despite promising results, the mechanisms by which psychedelic therapy may alleviate anxiety are not well understood. Here, we review neural and cognitive mechanisms underlying anxiety-related psychopathology and how psychedelics may impact these mechanisms. This review culminates in a tentative neurocognitive account of how psychedelics may promote long-term anxiolysis. We propose a model of anxiety related psychopathology wherein anxiety-related contextual information from the hippocampus may influence amygdala and salience network activity, biasing information processing toward anxiety-related content that thereby is encoded by the hippocampus and perpetuates this cycle. We posit that psychedelic may acutely free cortical networks from hippocampal-dependent contextual constraints in part through 5-HT_2A expression on excitatory and inhibitory neurons in the cortex and hippocampus, respectively, while the intrinsic plasticity of the hippocampus and/or psychedelic-mediated plasticity allows for a \"resetting of the hippocampal buffer.\" Following acute effects, increased cortical plasticity may enable the hippocampus to adaptively integrate novel information into a contextual frame less biased or constrained by prior aversive conditioning, promoting an overall reduction in anxious thoughts and appraisals. We end by discussing potential challenges of psychedelic therapy for anxiety, and suggest directions for future research to determine the optimal treatment paths informed by cognitive neuroscience.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nucleus accumbens CD81 regulates methamphetamine-induced locomotor activity, conditioned reward, and reinstatement in male and female rats.","authors":"Amine Bahi, Jean-Luc Dreyer","doi":"10.1007/s00213-026-07167-9","DOIUrl":"https://doi.org/10.1007/s00213-026-07167-9","url":null,"abstract":"<p><strong>Background: </strong>Methamphetamine (METH) use disorder is characterized by high rates of relapse and persistent neurobehavioral alterations. CD81, a member of the tetraspanin family, has been implicated in synaptic plasticity and addiction-related behaviors, but its role in METH-induced behavioral adaptations remains unknown.</p><p><strong>Aims: </strong>To determine whether METH-induced conditioned reward is associated with alterations in endogenous nucleus accumbens (NAcc) CD81 expression and to examine the effects of viral-mediated CD81 overexpression on METH-induced behavioral responses.</p><p><strong>Methods: </strong>Male and female rats underwent METH-induced conditioned place preference (CPP), after which endogenous CD81 mRNA expression was quantified in the NAcc. Based on these findings, separate cohorts received bilateral intra-accumbal injections of either control or CD81-expressing lentiviral vectors. The effects of CD81 overexpression on acute METH-induced locomotor activity, CPP acquisition, and METH-primed reinstatement following extinction were subsequently evaluated.</p><p><strong>Results: </strong>METH-conditioned animals exhibited significantly reduced accumbal CD81 mRNA expression, and endogenous CD81 levels were negatively correlated with CPP acquisition. Viral-mediated CD81 overexpression significantly attenuated METH-induced locomotor activation, reduced CPP acquisition, and suppressed METH-primed reinstatement following extinction. Accumbal CD81 mRNA expression was negatively correlated with locomotor activity, CPP magnitude, and reinstatement responses. Although females exhibited greater METH-induced locomotor activity than males, no significant sex differences were observed in CPP acquisition, reinstatement, or the behavioral effects of CD81 overexpression.</p><p><strong>Conclusions: </strong>Reduced endogenous CD81 expression in the NAcc is associated with METH reward learning, whereas restoration of CD81 expression attenuates METH-induced locomotor, rewarding, and relapse-like behaviors. These findings identify CD81 as a previously unrecognized regulator of METH-induced neurobehavioral adaptations and support a role for accumbal CD81 in addiction-related neuroplasticity.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148970478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anandamide blocks spatial memory reconsolidation in male rats through a CB1 receptor dependent mechanism.","authors":"Ruliam Queiroz, Crisleine Marchiori, Heitor Kraushaar Rosas, Isabella Sayuri Shiguehara Medeiros, Henrique Quilante Ferreira, Juliana Sartori Bonini, Weber Cláudio da Silva","doi":"10.1007/s00213-026-07161-1","DOIUrl":"https://doi.org/10.1007/s00213-026-07161-1","url":null,"abstract":"<p><strong>Background: </strong>Memory reconsolidation is a process through which previously consolidated memories become temporarily labile after retrieval and require molecular mechanisms, including protein synthesis and degradation, to be stabilized again. The endocannabinoid system, particularly cannabinoid receptors CB1 and CB2, has been implicated in several forms of learning and memory. However, the specific role of CB1 receptors in the regulation of protein turnover during spatial memory reconsolidation remains incompletely understood. Therefore, this study investigated whether cannabinoid receptor activation in the hippocampal CA1 region influences the reconsolidation of spatial memory.</p><p><strong>Methods: </strong>Spatial memory was evaluated using the Morris water maze task. After training, animals underwent an early non-reinforced test session 24 hours later to reactivate the previously acquired spatial memory. Immediately after this retrieval session, anandamide (AEA) or oleamide, a CB1 receptor agonist, was bilaterally infused into the CA1 region of the hippocampus. To investigate the involvement of CB1 receptors, some animals received a CB1 receptor antagonist together with the agonists. Additional experiments evaluated whether the amnesic effects of oleamide were dependent on protein degradation mechanisms and whether activation of CB1 receptors could modulate the effects produced by inhibition of protein synthesis.</p><p><strong>Results: </strong>Bilateral administration of AEA and oleamide into the hippocampal CA1 region immediately after memory retrieval impaired the reconsolidation of spatial memory, producing anterograde amnesia. Oleamide primarily affected the early long-term phase of spatial memory, whereas AEA impaired later phases of memory. The disruptive effect on memory reconsolidation was prevented by co-administration of a CB1 receptor antagonist, indicating that the observed effects were mediated by CB1 receptor activation. Furthermore, the amnesic effect induced by oleamide was dependent on protein degradation mechanisms. Conversely, the impairment caused by inhibition of protein synthesis could be reversed through inverse activation of CB1 receptors. These findings indicate an interaction between CB1 receptor signaling and the molecular mechanisms responsible for protein turnover during memory reconsolidation.</p><p><strong>Conclusion: </strong>The findings demonstrate that CB1 cannabinoid receptors in the hippocampal CA1 region play a direct role in the reconsolidation of spatial memory. Activation of these receptors can interfere with memory stabilization after retrieval by modulating protein degradation and protein synthesis mechanisms. Therefore, the endocannabinoid system, particularly CB1 receptor signaling, appears to be an important regulator of the molecular processes underlying the persistence and modification of long-term spatial memories.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148970178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topiramate effects on ethanol and sucrose binge-like intake, anxiety- and compulsive-like behavior in non-dependent male and female C57BL/6J mice.","authors":"Elisa Rodríguez-Ortega, Inmaculada Cubero","doi":"10.1007/s00213-026-07166-w","DOIUrl":"https://doi.org/10.1007/s00213-026-07166-w","url":null,"abstract":"<p><strong>Rationale: </strong>Repetitive binge episodes are early-stage patterns in the addiction cycle associated with elevated anxiety and compulsive traits. Despite their high comorbidity and the growing off-label use of topiramate for binge-related disorders, its effects in non-dependent individuals remain poorly characterized and studies systematically comparing both sexes under identical experimental conditions remain scarce.</p><p><strong>Objectives: </strong>To evaluate the effects of topiramate on ethanol (EtOH) and sucrose binge-like intake, anxiety- and compulsive-like responses in non-dependent male and female C57BL/6J mice.</p><p><strong>Methods: </strong>EtOH (20% v/v) and sucrose (10% w/v) binge-like intake were assessed in a standard Drinking in the Dark (DID) procedure following intraperitoneal topiramate (0, 30, or 60 mg/kg). Blood EtOH concentrations (BECs) were determined after EtOH DID. Anxiety-like and compulsive-like behaviors were assessed using the Elevated Plus Maze (EPM) and Marble Burying (MB) test.</p><p><strong>Results: </strong>Topiramate significantly reduced EtOH binge-like intake at 60 mg/kg and BECs at 30 and 60 mg/kg, while males consumed more EtOH and showed higher BECs than females. Topiramate did not significantly alter sucrose binge-like intake, with females consuming less sucrose than males. Topiramate significantly reduced anxiety-like behavior in the EPM regardless of sex. In the MB test, the topiramate effect differed significantly across sexes, although these results most likely reflect a floor effect in vehicle-treated females.</p><p><strong>Conclusions: </strong>These findings provide preliminary evidence that topiramate reduces EtOH binge-like intake, anxiety- and compulsive-like behavior in non-dependent mice with a non-significant attenuation of sucrose binge-like intake. Further research is warranted to establish the translational relevance and to evaluate the preventive potential of topiramate in binge-related disorders.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enantiomer-specific modulation of GABA_A receptors differentially regulates stress-induced dopamine dysregulation.","authors":"Kayla Lilly, Prithu Mondal, James M Cook, Stephanie M Perez, Daniel J Lodge","doi":"10.1007/s00213-026-07164-y","DOIUrl":"https://doi.org/10.1007/s00213-026-07164-y","url":null,"abstract":"<p><strong>Rationale: </strong>Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition that can emerge following exposure to severe trauma and is frequently accompanied by comorbid psychiatric symptoms, including psychosis. Hallucinations and delusions associated with PTSD are thought to arise from dysregulated mesolimbic dopamine signaling; however, converging evidence indicates dopamine dysfunction is secondary to hippocampal hyperactivity driven by impaired GABAergic transmission. An emerging pharmacological strategy is the use of positive allosteric modulators (PAMs) of GABA_A receptors. Given their dense expression within the hippocampus, receptors containing the α5 subunit (α5-GABA_ARs) have demonstrated antipsychotic-like efficacy across multiple preclinical models.</p><p><strong>Objectives: </strong>Whether this therapeutic potential reflects α-subunit specificity or broader properties of structurally related PAMs remains unclear. We compared three structurally related GABA_A receptor PAMs with distinct α-subunit selectivity.</p><p><strong>Methods: </strong>Using an acute inescapable footshock stress model, which reliably produces increased mesolimbic dopamine activity, we performed in vivo extracellular electrophysiology to record dopamine neuron activity in the ventral tegmental area (VTA) after intra-hippocampal administration of GABA_AR PAMs.</p><p><strong>Results: </strong>MP-III-022, a selective α5-GABA_AR PAM, normalized stress-induced elevations in VTA dopamine neuron population activity, consistent with prior reports. GL-I-54, which preferentially modulates α2/α3-GABA_ARs, failed to restore dopamine system function following stress, while modulation with the α5-preferring enantiomer GL-II-73 was associated with normalization of mesolimbic dopamine activity.</p><p><strong>Conclusions: </strong>These findings indicate that stereochemical and subunit-selective modulation of GABA_A receptors critically determines circuit-level outcomes following stress and reinforce α5-GABA_A receptors as a key target for normalizing hippocampal-driven dopamine system dysfunction associated with psychosis-relevant states.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148945602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concurrent chronic methamphetamine exposure may influence behavioral outcomes following repetitive mild traumatic brain injury.","authors":"Nicole M Hall, Peter H Seidenberg, Nicholas E Goeders","doi":"10.1007/s00213-026-07162-0","DOIUrl":"https://doi.org/10.1007/s00213-026-07162-0","url":null,"abstract":"<p><strong>Rationale: </strong>Traumatic brain injury (TBI) and substance use disorder (SUD) share several characteristics, including neurological outcomes and pathological traits. Misuse of stimulants, both non-prescription use of medications and illicit use of methamphetamine, is rising. Despite potential for misuse, stimulants are prescribed as treatment for some TBI-induced symptoms. Given that 40% of TBI patients have a history of SUD prior to injury, studies of the role that chronic substance misuse plays on the deleterious outcomes of TBI are warranted.</p><p><strong>Objectives: </strong>Our study explores the role that chronic methamphetamine exposure plays in the acute and long-term behavioral outcomes of repetitive mild TBI (rmTBI). We hypothesized that chronic methamphetamine exposure would exacerbate the behavioral deficits induced by rmTBI.</p><p><strong>Methods: </strong>We developed a model combining non-contingent dosing of methamphetamine with the Closed Head Model of Engineered Rotational Acceleration (CHIMERA). Behavioral assays were employed one month after the final TBI to assess short-term effects and were repeated six months following the final TBI for long-term effects.</p><p><strong>Results: </strong>The Loss of Righting Reflex showed that chronic methamphetamine exposure impacted neither TBI severity nor immediate recovery. The T-maze and NORT revealed that rmTBI concurrent to chronic methamphetamine exposure induced short- and long-term cognitive deficits. Methamphetamine negatively impacted balance and coordination on the accelerated rotarod at the later timepoint only.</p><p><strong>Conclusions: </strong>Together, these findings suggest that chronic methamphetamine exposure could potentially increase long-term, but not acute, TBI-induced deficits.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}