Psychopharmacology最新文献

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The effects of N-acetyl cysteine on intrinsic functional connectivity and neural alcohol cue reactivity in treatment-seeking individuals with alcohol use disorder: a preliminary study. N-乙酰半胱氨酸对寻求治疗的酒精使用障碍患者内在功能连接性和神经酒精线索反应性的影响:一项初步研究。
IF 3.5 3区 医学
Psychopharmacology Pub Date : 2024-08-05 DOI: 10.1007/s00213-024-06656-z
Warren B Logge, Paul S Haber, Tristan P Hurzeler, Ellen E Towers, Kirsten C Morley
{"title":"The effects of N-acetyl cysteine on intrinsic functional connectivity and neural alcohol cue reactivity in treatment-seeking individuals with alcohol use disorder: a preliminary study.","authors":"Warren B Logge, Paul S Haber, Tristan P Hurzeler, Ellen E Towers, Kirsten C Morley","doi":"10.1007/s00213-024-06656-z","DOIUrl":"https://doi.org/10.1007/s00213-024-06656-z","url":null,"abstract":"<p><p>N-acetyl cysteine (NAC) is a potential pharmacotherapy for alcohol use disorder (AUD), but it is not known whether it modulates neural activation to alcohol cues or intrinsic functional connectivity. We investigated whether NAC attenuates (i) alcohol cue-elicited activation, and (ii) intrinsic functional connectivity compared to placebo in patients with AUD. In this preliminary study, twenty-three individuals (7 females) with moderate-severe AUD received daily NAC (2400 mg/day, n = 9), or a placebo (n = 14) for at least 2 weeks. Participants completed a pre-treatment functional magnetic resonance imaging session (T0) and a post-treatment session (T1) comprising resting-state and visual alcohol cue reactivity task acquisitions. Activation differences between sessions, treatment, and session-by-treatment interaction were assessed. Resting-state functional connectivity examined using 377 node ROI-to-ROIs evaluated whether NAC reduced intrinsic functional connectivity after treatment. There were no differences in alcohol cue reactivity for brain activation or subjective craving between NAC and placebo during treatment or across sessions, or significant interaction. A significant treatment-by-time interaction, with reduced intrinsic connectivity was observed after treatment (T1) for NAC-treated compared to placebo-treated patients in the posterior cingulate node (9, left hemisphere) of the dorsal attentional network and connections to salience, ventral-attentional, somatosensory, and visual-peripheral networks implicated in AUD. NAC reduced intrinsic functional connectivity in patients with moderate-severe AUD after treatment compared to placebo, but did not attenuate alcohol cue-elicited activation. However, the absence of cue reactivity findings may result from low power, rather than the absence of cue reactivity findings associated with NAC. These results provide preliminary evidence that NAC treatment may modulate intrinsic functional connectivity brain activation in patients with alcohol use disorder, but replication in larger studies are required to determine the strength of this effect and any associations with clinical outcomes. Clinical Trials Registration: ClinicalTrials.gov Identifier: NCT03879759.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889999","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}
引用次数: 0
Unlocking new avenues for neuropsychiatric disease therapy: the emerging potential of Peroxisome proliferator-activated receptors as promising therapeutic targets. 开辟神经精神疾病治疗的新途径:过氧化物酶体增殖激活受体作为有前途的治疗靶点的新兴潜力。
IF 3.5 3区 医学
Psychopharmacology Pub Date : 2024-08-01 Epub Date: 2024-05-27 DOI: 10.1007/s00213-024-06617-6
Asmita Deka Dey, Ashi Mannan, Sonia Dhiman, Thakur Gurjeet Singh
{"title":"Unlocking new avenues for neuropsychiatric disease therapy: the emerging potential of Peroxisome proliferator-activated receptors as promising therapeutic targets.","authors":"Asmita Deka Dey, Ashi Mannan, Sonia Dhiman, Thakur Gurjeet Singh","doi":"10.1007/s00213-024-06617-6","DOIUrl":"10.1007/s00213-024-06617-6","url":null,"abstract":"<p><strong>Rationale: </strong>Peroxisome proliferator-activated receptors (PPARs) are transcription factors that regulate various physiological processes such as inflammation, lipid metabolism, and glucose homeostasis. Recent studies suggest that targeting PPARs could be beneficial in treating neuropsychiatric disorders by modulating neuronal function and signaling pathways in the brain. PPAR-α, PPAR-δ, and PPAR-γ have been found to play important roles in cognitive function, neuroinflammation, and neuroprotection. Dysregulation of PPARs has been associated with neuropsychiatric disorders like bipolar disorder, schizophrenia, major depression disorder, and autism spectrum disorder. The limitations and side effects of current treatments have prompted research to target PPARs as a promising novel therapeutic strategy. Preclinical and clinical studies have shown the potential of PPAR agonists and antagonists to improve symptoms associated with these disorders.</p><p><strong>Objective: </strong>This review aims to provide an overview of the current understanding of PPARs in neuropsychiatric disorders, their potential as therapeutic targets, and the challenges and future directions for developing PPAR-based therapies.</p><p><strong>Methods: </strong>An extensive literature review of various search engines like PubMed, Medline, Bentham, Scopus, and EMBASE (Elsevier) databases was carried out with the keywords \"PPAR, Neuropsychiatric disorders, Oxidative stress, Inflammation, Bipolar Disorder, Schizophrenia, Major depression disorder, Autism spectrum disorder, molecular pathway\".</p><p><strong>Result & conclusion: </strong>Although PPARs present a hopeful direction for innovative therapeutic approaches in neuropsychiatric conditions, additional research is required to address obstacles and convert this potential into clinically viable and individualized treatments.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154672","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}
引用次数: 0
Stimulus mediation, specificity and impact of menthol in rats trained to discriminate puffs of nicotine e-cigarette aerosol from nicotine-free aerosol. 训练大鼠分辨吸食尼古丁电子烟气雾剂和不含尼古丁的气雾剂时,薄荷醇的刺激介导、特异性和影响。
IF 3.5 3区 医学
Psychopharmacology Pub Date : 2024-08-01 Epub Date: 2024-03-23 DOI: 10.1007/s00213-024-06579-9
Yasmin Alkhlaif, Keith L Shelton
{"title":"Stimulus mediation, specificity and impact of menthol in rats trained to discriminate puffs of nicotine e-cigarette aerosol from nicotine-free aerosol.","authors":"Yasmin Alkhlaif, Keith L Shelton","doi":"10.1007/s00213-024-06579-9","DOIUrl":"10.1007/s00213-024-06579-9","url":null,"abstract":"<p><strong>Rationale: </strong>It is unclear if e-cigarettes have reduced abuse liability relative to traditional cigarettes, especially when considering advanced devices which deliver nicotine more efficiently. Translatable and predictive animal models are needed to addresses this question.</p><p><strong>Objectives: </strong>Our goal was to explore the subjective stimulus effects of e-cigarettes by training rats to discriminate puffs of nicotine aerosol from vehicle aerosol using an aerosol delivery system designed to model e-cigarette use patterns in humans.</p><p><strong>Methods: </strong>Rats were trained to discriminate between ten, 10 s puffs of aerosol generated from 3 mg/ml nicotine e-liquid and nicotine-free e-liquid using a food-reinforced operant procedure. Following acquisition, tests were conducted to determine the specificity of the nicotine aerosol stimulus as well as the impact to the stimulus effects of nicotine resulting from the addition of menthol to e-liquid.</p><p><strong>Results: </strong>Rats learned the nicotine aerosol puff vs vehicle puff discrimination in a mean of 25 training sessions. Injected nicotine fully substituted for the stimulus effects of nicotine aerosol. The stimulus effects of nicotine aerosol were blocked by the nicotinic receptor antagonist mecamylamine. The nicotinic receptor partial agonist, varenicline as well as the stimulant d-amphetamine substituted more robustly for nicotine aerosol puffs than did the NMDA antagonist, ketamine. Menthol enhanced the stimulus effects of nicotine aerosol without altering nicotine blood plasma levels.</p><p><strong>Conclusions: </strong>Nicotine aerosol puffs can function as a training stimulus in rats. The stimulus effects were CNS-mediated and receptor specific. Menthol appears to enhance the stimulus effects of nicotine aerosol through a pharmacodynamic rather than pharmacokinetic mechanism.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11269472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140194443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sex-dependent effects of acute stress in adolescence or adulthood on appetitive motivation. 青春期或成年期急性应激对食欲动机的影响与性别有关。
IF 3.5 3区 医学
Psychopharmacology Pub Date : 2024-08-01 Epub Date: 2024-05-16 DOI: 10.1007/s00213-024-06587-9
Rifka C Derman, K Matthew Lattal
{"title":"Sex-dependent effects of acute stress in adolescence or adulthood on appetitive motivation.","authors":"Rifka C Derman, K Matthew Lattal","doi":"10.1007/s00213-024-06587-9","DOIUrl":"10.1007/s00213-024-06587-9","url":null,"abstract":"<p><strong>Rationale: </strong>Intensely stressful experiences can lead to long-lasting changes in appetitive and aversive behaviors. In humans, post-traumatic stress disorder increases the risk of comorbid appetitive disorders including addiction and obesity. We have previously shown that an acute stressful experience in adult male rats suppresses motivation for natural reward.</p><p><strong>Objectives: </strong>We examine the impact of sex and age on the effects of intense stress on action-based (instrumental) and stimulus-based (Pavlovian) motivation for natural reward (food).</p><p><strong>Methods: </strong>Rats received 15 unsignaled footshocks (stress) in a single session followed by appetitive training and testing in a distinct context. In Experiment 1, stress occurred in either adolescence (PN28) or adulthood (PN70) with appetitive training and testing beginning on PN71 for all rats. In Experiment 2, stress and appetitive training/testing occurred in adolescence.</p><p><strong>Results: </strong>Acute stress in adolescent females suppressed instrumental motivation assessed with progressive ratio testing when testing occurred in late adolescence or in adulthood, whereas in males stress in adolescence did not suppress instrumental motivation. Acute stress in adulthood did not alter instrumental motivation. In contrast, Pavlovian motivation assessed with single-outcome Pavlovian-to-instrumental transfer (SO-PIT) was consistently enhanced in females following adolescent or adult stress. In males, however, stress in adolescence had no effect, whereas stress in adulthood attenuated SO-PIT.</p><p><strong>Conclusions: </strong>Acute stress in adolescence or adulthood altered instrumental motivation and stimulus-triggered Pavlovian motivation in a sex and developmentally specific manner. These findings suggest that the persistent effects of acute stress on Pavlovian and instrumental motivational processes differ in females and males, and that males may be less vulnerable to the deleterious effects of intense stress during adolescence on appetitive motivation.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945752","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}
引用次数: 0
Impact of aripiprazole discontinuation in remitted major depressive disorder: a randomized placebo-controlled trial. 阿立哌唑停药对缓解型重度抑郁症的影响:随机安慰剂对照试验。
IF 3.5 3区 医学
Psychopharmacology Pub Date : 2024-08-01 Epub Date: 2024-03-28 DOI: 10.1007/s00213-024-06581-1
Masahiro Takeshima, Akise Umakoshi, Yuki Omori, Kazuhisa Yoshizawa, Masaya Ogasawara, Mizuki Kudo, Yu Itoh, Naoko Ayabe, Kazuo Mishima
{"title":"Impact of aripiprazole discontinuation in remitted major depressive disorder: a randomized placebo-controlled trial.","authors":"Masahiro Takeshima, Akise Umakoshi, Yuki Omori, Kazuhisa Yoshizawa, Masaya Ogasawara, Mizuki Kudo, Yu Itoh, Naoko Ayabe, Kazuo Mishima","doi":"10.1007/s00213-024-06581-1","DOIUrl":"10.1007/s00213-024-06581-1","url":null,"abstract":"<p><strong>Rationale: </strong>The efficacy and safety of antidepressant augmentation therapy with aripiprazole (AATA) has been established; however, the ongoing effects of continuing aripiprazole after remission remain unclear because no studies have examined this issue.</p><p><strong>Objectives: </strong>We aimed to explore the effect of AATA discontinuation on the major depressive disorder (MDD) recurrence risk in patients with remitted MDD after AATA.</p><p><strong>Methods: </strong>This 24-week, multicenter, placebo-controlled, double-blind, randomized trial evaluated recurrence risk in patients with MDD who achieved remission with AATA. Differences in MDD recurrence, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, between the two groups were compared using survival analysis. The differences in depressive symptom severity and social functioning between the two groups were compared using a mixed model with repeated measures. Extrapyramidal symptoms and akathisia were also assessed.</p><p><strong>Results: </strong>Twenty-three participants were randomized and treated. Two patients in each group experienced recurrence during the study. Kaplan-Meier analysis with Log-rank comparison showed no difference in recurrence between groups (p = 0.642). No significant difference in interactions between group and period was observed in the 17-item Hamilton depression rating scale (p = 0.492) or the Social and Occupational Functioning Assessment Scale (p = 0.638). No patients developed extrapyramidal symptoms or akathisia.</p><p><strong>Conclusions: </strong>Definitive conclusions could not be drawn owing to the small sample size. This study represents a starting point for investigating the safety of aripiprazole discontinuation on recurrence in patients with MDD who have achieved remission with AATA. Future studies with appropriate sample sizes calculated based on this study are needed.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11269321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140306697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Adolescent alcohol binge drinking and withdrawal: behavioural, brain GFAP-positive astrocytes and acute methamphetamine effects in adult female rats. 青春期酗酒和戒酒:成年雌性大鼠的行为、大脑 GFAP 阳性星形胶质细胞和急性甲基苯丙胺效应。
IF 3.5 3区 医学
Psychopharmacology Pub Date : 2024-08-01 Epub Date: 2024-05-06 DOI: 10.1007/s00213-024-06580-2
Priscila A Costa, Nicholas A Everett, Anita J Turner, Laísa S Umpierrez, Sarah J Baracz, Jennifer L Cornish
{"title":"Adolescent alcohol binge drinking and withdrawal: behavioural, brain GFAP-positive astrocytes and acute methamphetamine effects in adult female rats.","authors":"Priscila A Costa, Nicholas A Everett, Anita J Turner, Laísa S Umpierrez, Sarah J Baracz, Jennifer L Cornish","doi":"10.1007/s00213-024-06580-2","DOIUrl":"10.1007/s00213-024-06580-2","url":null,"abstract":"<p><strong>Rationale: </strong>Alcopop beverages are generally the first alcoholic beverage that young females drink which contain high levels of sugar and alcohol. The over-consumption of these drinks may encourage alcohol co-administration with methamphetamine (METH) impacting on drinking behaviour and glial function.</p><p><strong>Aims: </strong>The aims of this study were to evaluate the effect of adolescent binge alcohol exposure on consumption level, anxiety-like behaviour, cross-sensitization with METH and on astrocyte expression in reward related brain regions.</p><p><strong>Methods: </strong>Adolescent female Sprague-Dawley rats had daily 1-hour oral alcohol consumption of alcopop (ALCP; with sucrose) or ethanol-only (ETOH; without sucrose), transitioned from 5 to 15% (v/v) ethanol content for 34 days. Water and sucrose groups act as controls. During alcohol withdrawal, rats were tested for anxiety on the elevated plus maze (EPM) and locomotor activity following saline or METH (1 mg/kg i.p) treatment. Brains were then collected to assess astrocyte immunofluorescence for glial fibrillary acidic protein (GFAP) in reward-related brain regions.</p><p><strong>Results: </strong>Rats pretreated with 5% ALCP consumed significantly more volume and ethanol intake when compared to 5% EtOH rats. Both ALCP and EtOH groups had a higher preference ratio for 5% than 15% alcohol solutions and ALCP rats had greater ethanol intake at 15% than EtOH rats. Alcohol withdrawal showed no significant differences between groups on anxiety, METH cross-sensitization effects or GFAP intensity in the regions studied.</p><p><strong>Conclusions: </strong>Overall, the addition of sucrose to alcoholic solutions encouraged female rats to consume larger volumes and greater ethanol intake compared to ethanol-only solutions, yet did not have long lasting effects on behaviour and astrocytes.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11269403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140871107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Psychedelic-assisted psychotherapy: where is the psychotherapy research? 迷幻药辅助心理疗法:心理疗法研究在哪里?
IF 3.5 3区 医学
Psychopharmacology Pub Date : 2024-08-01 Epub Date: 2024-05-24 DOI: 10.1007/s00213-024-06620-x
Jacob S Aday, David Horton, Gisele Fernandes-Osterhold, Aoife O'Donovan, Ellen R Bradley, Raymond C Rosen, Joshua D Woolley
{"title":"Psychedelic-assisted psychotherapy: where is the psychotherapy research?","authors":"Jacob S Aday, David Horton, Gisele Fernandes-Osterhold, Aoife O'Donovan, Ellen R Bradley, Raymond C Rosen, Joshua D Woolley","doi":"10.1007/s00213-024-06620-x","DOIUrl":"10.1007/s00213-024-06620-x","url":null,"abstract":"<p><strong>Rationale: </strong>Psychedelic-assisted psychotherapy (PAP) has emerged as a potential treatment for a variety of mental health conditions, including substance use disorders and depression. Current models of PAP emphasize the importance of psychotherapeutic support before, during, and after ingestion of a psychedelic to maximize safety and clinical benefit. Despite this ubiquitous assumption, there has been surprisingly little empirical investigation of the \"psychotherapy\" in PAP, leaving critical questions about the necessary and sufficient components of PAP unanswered.</p><p><strong>Objectives: </strong>As clinical trials for psychedelic compounds continue the transition from safety- and feasibility-testing to evaluating efficacy, the role of the accompanying psychotherapy must be better understood to enhance scientific understanding of the mechanisms underlying therapeutic change, optimize clinical outcomes, and inform cost-effectiveness.</p><p><strong>Results: </strong>The present paper first reviews the current status of psychotherapy in the PAP literature, starting with recent debates regarding \"psychotherapy\" versus \"psychological support\" and then overviewing published clinical trial psychotherapy models and putative models informed by theory. We then delineate lessons that PAP researchers can leverage from traditional psychotherapy research regarding standardizing treatments (e.g., publish treatment manuals, establish eligibility criteria for providers), identifying mechanisms of change (e.g., measure established mechanisms in psychotherapy), and optimizing clinical trial designs (e.g., consider dismantling studies, comparative efficacy trials, and cross-lagged panel designs). Throughout this review, the need for increased research into the psychotherapeutic components of treatment in PAP is underscored.</p><p><strong>Conclusions: </strong>PAP is a distinct, integrative, and transdisciplinary intervention. Future research designs should consider transdisciplinary research methodologies to identify best practices and inform federal guidelines for PAP administration.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086917","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}
引用次数: 0
Sex differences in morphine sensitivity of neuroligin-3 knockout mice. 神经胶质蛋白-3基因敲除小鼠对吗啡敏感性的性别差异。
IF 3.5 3区 医学
Psychopharmacology Pub Date : 2024-07-31 DOI: 10.1007/s00213-024-06660-3
Dieter D Brandner, Mohammed A Mashal, Nicola M Grissom, Patrick E Rothwell
{"title":"Sex differences in morphine sensitivity of neuroligin-3 knockout mice.","authors":"Dieter D Brandner, Mohammed A Mashal, Nicola M Grissom, Patrick E Rothwell","doi":"10.1007/s00213-024-06660-3","DOIUrl":"10.1007/s00213-024-06660-3","url":null,"abstract":"<p><p>Sex has a strong influence on the prevalence and course of brain conditions, including autism spectrum disorders. The mechanistic basis for these sex differences remains poorly understood, due in part to historical bias in biomedical research favoring analysis of male subjects, and the exclusion of female subjects. For example, studies of male mice carrying autism-associated mutations in neuroligin-3 are over-represented in the literature, including our own prior work showing diminished responses to chronic morphine exposure in male neuroligin-3 knockout mice. We therefore studied how constitutive and conditional genetic knockout of neuroligin-3 affects morphine sensitivity of female mice, using locomotor activity as a proxy for differences in opioid sensitivity that may be related to the pathophysiology and treatment of autism spectrum disorders. In contrast to male mice, female neuroligin-3 knockout mice showed normal psychomotor sensitization after chronic morphine exposure. However, in the absence of neuroligin-3 expression, both female and male mice show a similar change in the topography of locomotor stimulation produced by morphine. Conditional genetic deletion of neuroligin-3 from dopamine neurons increased the locomotor response of female mice to high doses of morphine, contrasting with the decrease in psychomotor sensitization caused by the same manipulation in male mice. Together, our data reveal that knockout of neuroligin-3 has both common and distinct effects on morphine sensitivity in female and male mice. These results also support the notion that female sex can confer resilience against the impact of autism-associated gene variants.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856294","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}
引用次数: 0
Increased risky choice during forced abstinence from fentanyl on the cued rat gambling task. 在强迫戒除芬太尼期间,在大鼠赌博任务中的风险选择增加。
IF 3.5 3区 医学
Psychopharmacology Pub Date : 2024-07-30 DOI: 10.1007/s00213-024-06659-w
Kelly M Hrelja, Carol Kawkab, Dimitrios K Avramidis, Shrishti Ramaiah, Catharine A Winstanley
{"title":"Increased risky choice during forced abstinence from fentanyl on the cued rat gambling task.","authors":"Kelly M Hrelja, Carol Kawkab, Dimitrios K Avramidis, Shrishti Ramaiah, Catharine A Winstanley","doi":"10.1007/s00213-024-06659-w","DOIUrl":"https://doi.org/10.1007/s00213-024-06659-w","url":null,"abstract":"<p><strong>Rationale: </strong>The use of illicit opioids has arguably never been more risky; street drug potency can be dangerously high, is often unknown to the consumer, and results in multiple daily fatalities worldwide. Furthermore, substance use disorder (SUD) is associated with increased maladaptive, risky decisions in laboratory-based gambling tasks. Animal studies can help determine whether this decision-making deficit is a cause or consequence of drug use. However, most experiments have only assessed psychostimulant drugs.</p><p><strong>Objectives: </strong>To assess differences in decision-making strategies both before, during, and after self-administration of fentanyl in male and female Long Evans rats.</p><p><strong>Methods: </strong>Male and female Long Evans rats were trained to perform the rat gambling task (rGT), loosely based on the Iowa Gambling Task (IGT) used clinically, and/or self-administer fentanyl. We used the cued version of the rGT, in which sound and light stimuli signal sugar pellet rewards, as cocaine self-administration has the greatest effects on decision making in this task variant.</p><p><strong>Results: </strong>After training on the cued rGT, female rats self-administered fentanyl more readily, an effect that was most apparent in optimal decision-makers. Contrary to previous reports using cocaine self-administration, decision-making was unaffected during fentanyl self-administration training in either sex. However, risky decision-making increased throughout forced abstinence from fentanyl in males.</p><p><strong>Conclusions: </strong>These findings complement those from human subjects, in whom preference for uncertain outcomes increased before relapse. These data highlight an abstinence-induced change in cognition that is unique to opiates as compared to psychostimulants, and which may critically contribute to the maintenance of addiction and relapse.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793193","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}
引用次数: 0
Correction to: 17β-Estradiol augments the neuroprotective effect of agomelatine in depressive- and anxiety-like behaviors in ovariectomized rats 更正为17β-雌二醇增强阿戈美拉汀对卵巢切除大鼠抑郁和焦虑行为的神经保护作用
IF 3.4 3区 医学
Psychopharmacology Pub Date : 2024-07-27 DOI: 10.1007/s00213-024-06655-0
Yasmine A. El-Khatib, Rabab H. Sayed, Nada A. Sallam, Hala F. Zaki, Mahmoud M. Khattab
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