Psychopharmacology最新文献

{"title":"Effects of TPA023B, an α2/3/5GABA_A subtype-selective partial allosteric modulator, on fentanyl-induced respiratory depression in male rats: comparison with the non-selective benzodiazepine midazolam.","authors":"Loc M Pham, Andria B Nanney, Jordan Hasting, Daniela Rüedi-Bettschen, Kevin B Freeman, James K Rowlett","doi":"10.1007/s00213-025-06945-1","DOIUrl":"10.1007/s00213-025-06945-1","url":null,"abstract":"<p><strong>Rationale: </strong>Opioid-related overdose deaths involving benzodiazepines have increased in recent years, and prior studies have reported that clinically used benzodiazepines can enhance the respiratory-depressant effects of mu opioid receptor (MOR) agonists. TPA023B is an α1-sparing GABA_A positive allosteric modulator developed as a potential anxiolytic with fewer benzodiazepine-typical side effects. However, it is unknown if and to what degree TPA023B can affect MOR-agonist induced respiratory depression.</p><p><strong>Objectives: </strong>The current study compared the effects of either TPA023B or midazolam, alone and combined with fentanyl, on respiratory depression in rats, using whole-body plethysmography.</p><p><strong>Methods: </strong>Male Sprague-Dawley rats were implanted with chronic indwelling intravenous (i.v.) catheters for drug infusions. Respiration (frequency, tidal volume, and minute volume) was measured using whole-body plethysmography. The tests consisted of a pretreatment (midazolam, 30 mg/kg; i.v.; TPA023B, 1.0 mg/kg; i.v; or vehicle) followed by a fentanyl injection (0.01, 0.03, 0.1 mg/kg, i.v., or vehicle) and 60 min of respiration assessment.</p><p><strong>Results: </strong>Overall, fentanyl alone, but not TPA023B or midazolam alone, produced dose-dependent reductions in tidal volume and minute volume. When administered as pre-treatments, neither midazolam nor TPA023B increased the magnitude of fentanyl-induced respiratory depression, instead producing prolonged reductions in tidal volume and minute volume. Midazolam produced a more sustained reduction in these parameters than TPA023B.</p><p><strong>Conclusions: </strong>Benzodiazepines prolong fentanyl-induced respiratory depression, but this effect may be reduced by eliminating activity at α1GABA_A receptor subtypes.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2019-2028"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13370654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145422584","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}

{"title":"Effects of delta-9 tetrahydrocannabinol and cannabidiol on cognitive outcomes following acute use of cannabis for chronic pain.","authors":"Renée Martin-Willett, Samantha N Melendez, Kent E Hutchison, Angela D Bryan, L Cinnamon Bidwell","doi":"10.1007/s00213-026-07157-x","DOIUrl":"https://doi.org/10.1007/s00213-026-07157-x","url":null,"abstract":"<p><strong>Rationale: </strong>An estimated two-thirds of medical cannabis users in the United States are motivated by chronic pain, but clinical guidance remains guarded as to whether the potential benefit of cannabinoids for pain outweighs potential risks, such as effects on cognition.</p><p><strong>Objectives: </strong>In a study where participants experienced benefits of cannabinoids for pain and tension, we evaluated cannabis effects on executive function, processing speed, memory, and verbal learning following acute use for chronic, non-specific low back pain.</p><p><strong>Methods: </strong>Participants were in one of three self-selected edible cannabis groups: a) CBD-dominant, b) THC-dominant, or c) a mixed ratio of CBD to THC and completed a battery of cognitive tasks at pre-use, 1 h post-use use, and 2 h post-use.</p><p><strong>Results: </strong>Among 183 participants (56.8% female; M_age = 45.6), those in the group using CBD outperformed participants using CBD + THC 1 h post use in working memory and produced more stable scores in verbal learning after use than participants using THC or CBD + THC. Additionally, while older age was associated with better working memory in the CBD group before use, that relationship was progressively attenuated over the subsequent timepoints. There were no significant effects of cannabis use on cognition in the domains of executive function, episodic memory, or processing speed.</p><p><strong>Conclusions: </strong>Given the ubiquity of cannabis use for chronic pain and the ongoing call for more data, this study is relevant for informing clinical guidance on whether, and how, cannabis could be used in this context. In particular, understanding the acute impact on cognition from cannabis is critical, as cognitive functioning directly affects patients' daily lives and quality of life.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148876034","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":"Electroacupuncture alleviates depressive symptoms in post-stroke depression rat models by AMPK-mediated mitochondrial pathway.","authors":"Jiang He, Donghui Yang, Ying Ye, Xianfen Zhu","doi":"10.1007/s00213-025-06955-z","DOIUrl":"10.1007/s00213-025-06955-z","url":null,"abstract":"","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2099-2109"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181880","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":"Personality profiles and trauma history in ketamine therapy for mood and anxiety disorders: A latent profile analysis of short-term outcomes.","authors":"Nina Gregoire, Ethan Klukas, Kimberley Kaseweter, W Francois Louw, Paul G Davies","doi":"10.1007/s00213-025-06948-y","DOIUrl":"10.1007/s00213-025-06948-y","url":null,"abstract":"<p><strong>Rationale: </strong>Ketamine-assisted therapy is emerging as a fast-acting intervention for treatment-resistant depression and anxiety. However, individual response to treatment varies, and little is known about how personality traits and trauma history influence outcomes.</p><p><strong>Objectives: </strong>This study investigated whether distinct personality profiles emerge in a real-world sample of patients undergoing ketamine therapy and examined how these profiles, along with trauma history, relate to baseline symptoms and short-term treatment outcomes.</p><p><strong>Methods: </strong>A total of 184 patients seeking ketamine-assisted therapy at a Canadian clinic completed baseline assessments, including the Mini-IPIP (personality), PHQ-9 (depression), GAD-7 (anxiety), and WHOQOL-BREF (quality of life). Latent profile analysis (LPA) was used to identify personality-based subgroups. Paired-sample t-tests and ANOVAs were conducted to examine differences in symptom severity and change scores after treatment.</p><p><strong>Results: </strong>Three personality profiles were identified: Easygoing Extraverts, Average, and Reserved Introverts. Reserved Introverts reported significantly higher baseline depression and anxiety than other profiles. While all profiles showed improvements in depression and anxiety one-week post-treatment, the personality profiles did not predict differential symptom change. However, participants with a trauma history showed greater reductions in depression and improvements in physical quality of life than those without.</p><p><strong>Conclusions: </strong>Personality traits relate to baseline mental health severity but not short-term response to ketamine. Trauma history may predict greater benefit from treatment. These findings support further integration of personality and trauma assessments into personalized care approaches.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2043-2054"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145378551","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":"7,8-Dihydroxyflavone ameliorates bone loss by regulating TRKB/AKT/FOXO3a pathway in a mouse model of alzheimer's disease.","authors":"Dong Liu, Xiaoxiong Li, Peng Shi, Wenjuan Hong, Jie Huang, Mingliang Hou, Linqiu Ma, Qirong Liao, Hongyan Yang, Xiaoyan Fu, Huadong Zhou, Jing Lu, Yating Liu, Xiangqian Feng, Donglin Wang, Rui Zhou","doi":"10.1007/s00213-025-06957-x","DOIUrl":"10.1007/s00213-025-06957-x","url":null,"abstract":"<p><strong>Background: </strong>The incidence of osteoporosis is increased in Alzheimer's disease (AD). The pathogenesis of AD with osteoporosis is still unknown, there is no ideal treatment as yet for it. 7,8-Dihydroxyflavone (7,8-DHF), a functional brain-derived neurotrophic factor (BDNF) mimetic, shows therapeutic potential for neurological and orthopedic disorders.</p><p><strong>Objectives: </strong>This research investigated the molecular mechanisms by which 7,8-DHF mitigates bone loss and cognitive dysfunction in osteoporotic AD mice.</p><p><strong>Methods: </strong>Micro-CT analysis quantified bone loss in AD mice. The Morris water maze (MWM) assessed mouse cognitive function, and immunohistochemical analysis measured Aβ plaque deposition. qPCR and Western blotting measured expression levels of APP, Aβ42, TRKB, and FOXO3a in osteoblasts isolated from femoral bone marrow mesenchymal stem cells (BMSCs) and brain tissue. ELISA determined the levels of IL-1β, IL-6, osteocalcin (OCN), fibroblast growth factor 23 (FGF23) and sclerostin. For in vitro experiments, osteoblast differentiation was monitored in MC3T3-E1 cells co-cultured with Aβ42, with concurrent measurement of TRKB, AKT, and FOXO3a expression. The efficacy of 7,8-DHF against bone loss and osteoblast differentiation was systematically evaluated.</p><p><strong>Results: </strong>Cognitive impairment and bone loss manifested in APP/PS1 mice. 7,8-DHF treatment ameliorated bone mass reduction, decreased Aβ42 expression in bone tissue, and enhanced TRKB expression. Concurrently, 7,8-DHF improved cognitive function and accelerated clearance of [¹²⁵I]-Aβ42 from the brain. In in-vitro, Aβ42 increased inflammatory cytokine levels, suppressed TRKB expression, and impaired osteoblast differentiation. 7,8-DHF reduced the levels of AKT and pFOXO3a by TRKB.</p><p><strong>Conclusion: </strong>7,8-DHF could alleviate bone mass loss in AD mice by regulating the TRKB/AKT/FOXO3a pathway. This finding provides new ideas for the treatment strategy of AD with osteoporosis and is beneficial to the health of the elderly.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2111-2129"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687858","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":"Cannabidiol and neural correlates of threat anticipation in alcohol use disorder.","authors":"Tristan Hurzeler, Warren Logge, Joshua Watt, Iain McGregor, Anastasia Suraev, Paul S Haber, Kirsten C Morley","doi":"10.1007/s00213-026-07148-y","DOIUrl":"https://doi.org/10.1007/s00213-026-07148-y","url":null,"abstract":"<p><strong>Rationale: </strong>Cannabidiol (CBD) has previously been suggested to be an emerging pharmacotherapy for Alcohol Use Disorder (AUD), however, results from clinical studies remain mixed and potential mechanisms remain elusive.</p><p><strong>Objectives: </strong>The aim of the present study is to investigate the potential for CBD to modulate neurobiological, cognitive and psychological processes during anticipation of threatening stimuli.</p><p><strong>Methods: </strong>In a cross-over, double-blind, randomized trial, non-treatment seeking individuals diagnosed with AUD (DSM-V) were recruited to receive either 800mg of CBD or matched placebo, completing two respective fMRI sessions. Region of interest (ROI) and whole-brain analysis were utilized to examine treatment effects on neural activity in response to high vs low threat anticipation stimuli during a fear anticipation continuous performance task (FCPT).</p><p><strong>Results: </strong>Sixteen participants contributed complete FCPT data and fourteen contributed analysable fMRI data. No main treatment effects were observed across cognition, regional or whole-brain activation. Drinking the day before the scan was associated with longer latencies in responses on the continuous performance task.</p><p><strong>Conclusion: </strong>The present findings indicate that CBD did not produce measurable effects on brain activity or cognitive performance during threat anticipation in individuals with AUD suggesting that previously reported neural effects may be more closely related to direct responses to salient stimuli rather than anticipatory processes.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148875853","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":"Impaired contingency judgement in mice under ketamine: an implication for an altered sense of agency in schizophrenia.","authors":"Riria Suzuki, Yutaka Kosaki","doi":"10.1007/s00213-025-06954-0","DOIUrl":"10.1007/s00213-025-06954-0","url":null,"abstract":"","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2085-2097"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794630","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":"Glymphatic system dysfunction: a link between sleep disorders and neurodegeneration.","authors":"Huiran Yang, Xin Tian, Xiaomeng Luo, Zhanchao Chang, Peipei Li","doi":"10.1007/s00213-026-07004-z","DOIUrl":"10.1007/s00213-026-07004-z","url":null,"abstract":"<p><strong>Rationale: </strong>Sleep disturbances are closely associated with cognitive decline and an increased risk of neurodegenerative diseases in humans. This association may be mediated by glymphatic dysfunction, which could ultimately lead to cognitive deterioration.</p><p><strong>Objectives: </strong>This review aims to provide an overview of current research on the impact of sleep on the functions of the glymphatic system. It analyzes the regulatory roles of the sleep-wake cycle and neurovascular coupling (NVC), along with molecular mechanisms such as astrocytic calcium signaling and aquaporin-4 (AQP4) polarization, intending to identify potential targets for preventing and alleviating cognitive decline and neurodegenerative diseases.</p><p><strong>Results: </strong>This review summarizes the intrinsic mechanisms by which sleep regulates the metabolic waste clearance capacity of the glymphatic system, highlighting its central role in regulating glymphatic function. Furthermore, it provides a detailed overview of the significant contributions of NVC and astrocytes within this regulatory framework, as well as novel interventions targeting neurodegenerative diseases.</p><p><strong>Conclusions: </strong>Given that sleep disturbances are a significant factor affecting human cognitive function and neurodegenerative diseases, it is imperative to advance research in this field. Efforts should focus on deepening our understanding of the glymphatic system and its regulatory mechanisms while integrating clinical practice to explore new research directions.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"1985-2003"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146041567","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":"Optogenetic stimulation of the infralimbic cortex prior to fear extinction learning rescues deficits in a preclinical model of comorbid PTSD and AUD.","authors":"Liza J Wills, Bailey Adams, Britta Schwartz, Eric Beaumont, Justin T Gass","doi":"10.1007/s00213-025-06960-2","DOIUrl":"10.1007/s00213-025-06960-2","url":null,"abstract":"<p><strong>Rationale: </strong>Post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) frequently co-occur, leading to significant impairments in learning and memory. Despite the prevalence of these disorders, existing treatment strategies remain inadequate, necessitating novel approaches targeting underlying neural circuits.</p><p><strong>Objectives: </strong>This study investigated whether optogenetic stimulation of medial prefrontal cortex subregions could rescue fear extinction deficits in a preclinical model of comorbid PTSD/AUD. We examined the differential roles of the infralimbic (IL) and prelimbic (PL) cortices in modulating extinction learning following combined stress and chronic alcohol exposure.</p><p><strong>Methods: </strong>Male and female Wistar rats underwent restraint stress (RS) and chronic intermittent ethanol exposure (CIE), followed by fear conditioning and extinction training. Animals received optogenetic stimulation (ChR2 or eYFP control) targeting either IL or PL cortex immediately prior to each extinction session. Extinction learning rates, days to criterion, and long-term memory retention (21-day spontaneous recovery) were assessed.</p><p><strong>Results: </strong>Combined stress and alcohol exposure significantly impaired extinction learning compared to controls. IL-ChR2 stimulation recovered these extinction deficits in the RS + CIE group, accelerating extinction rates and reducing spontaneous recovery. Conversely, PL-ChR2 stimulation impaired extinction learning in control animals but produced no additional deficits in the already-impaired RS + CIE group, suggesting a ceiling effect.</p><p><strong>Conclusions: </strong>This study identifies the IL cortex as a critical regulator of fear extinction learning following stress and alcohol exposure, demonstrating that targeted circuit activation can overcome extinction deficits characteristic of comorbid PTSD and AUD. These region-specific effects provide important insights into the prefrontal mechanisms governing fear memory processes in pathological states.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2143-2163"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145471847","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":"Behavioral impact of chemogenetic manipulations of 5-HT DRN neurons in transgenic Tph2-iCre rats.","authors":"Nicholas S McCloskey, Chen Li, Lynn G Kirby","doi":"10.1007/s00213-025-06947-z","DOIUrl":"10.1007/s00213-025-06947-z","url":null,"abstract":"<p><strong>Rationale: </strong>Our laboratory has demonstrated that stressors regulate the 5-HT system with consequences in behavioral models of psychiatric disorders including addiction. We have employed behavioral pharmacology methods to show that stressors engage corticotropin-releasing factor afferents to 5-HT dorsal raphe nucleus (DRN) neurons with effects on negative affective state and stress-induced opioid relapse models. Given the ongoing opioid crisis, there remains a need to elucidate the neural mechanisms underlying opioid use disorder with molecular, temporal and spatial precision using newer circuit manipulation strategies in animal models.</p><p><strong>Objectives: </strong>We sought to characterize the behavioral effects of chemogenetic manipulations of 5-HT DRN neurons in male and female Tph2-iCre rats.</p><p><strong>Methods: </strong>Subjects received intra-DRN viral infusions of Cre-dependent inhibitory or excitatory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). Three behavioral paradigms were used to examine the effect of clozapine-N-oxide activation or inhibition of 5-HT DRN neurons: elevated plus maze (EPM), forced swim test (FST), and stress-induced reinstatement of morphine conditioned place preference (CPP).</p><p><strong>Results: </strong>Chemogenetic activation of 5-HT DRN neurons induces anxiety-like behavior in the EPM in a transgenic rat model.</p><p><strong>Conclusions: </strong>This study confirms some of the findings of prior chemo- and optogenetic studies in mice showing a role of 5-HT DRN neurons in anxiety-like behaviors but did not support effects in the FST model or in reinstatement of morphine CPP. Given the growing availability of transgenic rat lines, future studies in transgenic rats are needed to help dissect a complex literature on the behavioral functions of the 5-HT system.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2029-2041"},"PeriodicalIF":3.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12958828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145524210","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}