Psychopharmacology最新文献

{"title":"A prospective ecological momentary assessment study of an ayahuasca retreat: exploring the salutary impact of acute psychedelic experiences on subacute affect and mindfulness skills in daily life.","authors":"Sharon R Sznitman, Yoel A Behar, Sheila Daniela Dicker-Oren, Tamar Shochat, David Meiri, Nader Butto, David Roe, Amit Bernstein","doi":"10.1007/s00213-024-06704-8","DOIUrl":"https://doi.org/10.1007/s00213-024-06704-8","url":null,"abstract":"<p><strong>Rationale: </strong>To examine the acute effects of ayahuasca use and their relationship to sub-acute changes in affect and mindfulness in a non-clinical sample, addressing the need for a better understanding of ayahuasca's immediate and short-term impacts as interest in its use grows.</p><p><strong>Objectives: </strong>Using prospective ecological assessment, this study investigates how ayahuasca used at a 4-day retreat affects positive/negative affect and mindfulness skills in daily living compared to pre-retreat. Additionally, we explore acute psychedelic experiences during the ayahuasca retreat, assessed retrospectively 1-2 days post-retreat, as potential mechanisms for theorized effects in daily living post-retreat.</p><p><strong>Methods: </strong>Thirty-six participants reported positive/negative affect and mindfulness skills three times daily for 5 days before and after the retreat. Baseline assessments included lifetime psychedelic experience, and post-retreat assessments covered acute ayahuasca experiences. Mixed-effect linear models were used to analyze the data.</p><p><strong>Results: </strong>Post-retreat, we observed reduced negative affect, increased positive affect, and enhanced mindfulness skills in daily living. Ayahuasca-induced acute experiences, such as time/space transcendence, emotional breakthrough and challenging experiences predicted greater subacute positive affect. Notably, none of these experiences were linked to subacute improvements in negative affect or mindfulness. No participants showed clinically significant adverse responses post-retreat, and only 5.5% exhibited some degree of potentially clinically significant deterioration in affect.</p><p><strong>Conclusions: </strong>Ayahuasca use may lead to improvement in mood and mindfulness skills, and key acute psychedelic experiences induced by ayahuasca may be important to some of these salutary effects, positive affect in particular.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010585","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":"Captopril attenuates oxidative stress and neuroinflammation implicated in cisplatin-induced cognitive deficits in rats.","authors":"Fatma Mostafa, Eman M Mantawy, Riham S Said, Samar S Azab, Ebtehal El-Demerdash","doi":"10.1007/s00213-024-06706-6","DOIUrl":"https://doi.org/10.1007/s00213-024-06706-6","url":null,"abstract":"<p><strong>Rationale: </strong>One of the most debilitating drawbacks of cisplatin chemotherapy is neurotoxicity which elicits memory impairment and cognitive dysfunction (chemobrain). This is primarily triggered by oxidative stress and inflammation. Captopril, an angiotensin-converting enzyme inhibitor, has been reported as a neuroprotective agent owing to its antioxidant and anti-inflammatory effects.</p><p><strong>Objective: </strong>We examined the possible neuroprotective effect of captopril against cisplatin-induced neurological and behavioral abnormalities in rats.</p><p><strong>Methods: </strong>Chemobrain was induced in rats by cisplatin (5 mg/kg, i.p.) on the 7th and 14th days of the study while captopril was administered orally (25 mg/kg) daily for three weeks. The effects of captopril were assessed by performing behavioral tests, histological examination, and evaluation of oxidative stress and inflammatory markers.</p><p><strong>Results: </strong>Cisplatin caused learning/memory dysfunction assessed by passive avoidance and Y-maze tests, decline in locomotion, and rotarod motor balance loss which were further verified by neurodegeneration observed in histological examination. Also, cisplatin aggravated oxidative stress by elevating lipid peroxidation (MDA) levels and diminishing catalase activity. Moreover, cisplatin upregulated the neuroinflammatory markers (TNF, IL-6, GFAP, and NF-κB). Captopril successfully ameliorated cisplatin damage on the levels of neurobehavioral and histopathological changes. Mechanistically, captopril significantly diminished MDA production and preserved catalase antioxidant activity. Captopril also counteracted neuroinflammation through inhibiting NF-κB and its downstream proinflammatory cytokines besides repressing astrocyte activity by reducing GFAP expression.</p><p><strong>Conclusion: </strong>Our findings revealed that captopril could abrogate cisplatin neurotoxicity via reducing oxidative stress and neuroinflammation thus enhancing cognitive and behavioral performance. This could suggest the repurposing of captopril as a neuroprotective agent, especially in hypertensive cancer patients receiving cisplatin.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984615","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":"Poly ADP-ribosylation regulates Arc expression and promotes adaptive stress-coping.","authors":"Eliyahu Dahan, Leah Pergamenshik, Tze'ela Taub, Arthur Vovk, Jade Manier, Raphael Avneri, Elad Lax","doi":"10.1007/s00213-025-06744-8","DOIUrl":"https://doi.org/10.1007/s00213-025-06744-8","url":null,"abstract":"<p><strong>Rationale: </strong>Rapid adaptation to stressful events is essential for survival and requires acute stress response and stress-coping strategy. However, the molecular mechanisms that govern this coping strategy have yet to be fully discovered.</p><p><strong>Objectives: </strong>This study aims to investigate the effects of poly ADP-ribosylation (PARylation) on stress-coping strategies following acute stress and to identify the target genes influenced by Parp1-induced histone PARylation.</p><p><strong>Methods: </strong>Mice were subjected to a forced swim test, a well-established acute stress paradigm, to evaluate cortical PARylation and assess the expression of activity-dependent genes. The pharmacological inhibition of Parp1 was conducted using ABT888 (Veliparib) to determine its effects on stress-coping behavior and related molecular changes.</p><p><strong>Results: </strong>The forced swim test increased cortical PARylation and upregulated the expression of activity-dependent genes. Systemic inhibition of Parp1 with ABT888 led to impaired stress-coping behavior, evidenced by a reduced immobility response during a subsequent forced swim test done 24 hours later. This impairment was associated with decreased chromatin PARylation and histone H4 acetylation at the Arc promoter and reduced Arc expression observed one hour after Parp1 inhibition.</p><p><strong>Conclusion: </strong>Our findings indicate that chromatin PARylation at the Arc promoters regulates histone H4 acetylation and Arc gene expression, and a subsequent impact on successful stress-coping behavior in response to acute stress.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979869","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":"Investigating the role of GPR39 in treatment of stress-induced depression and anxiety.","authors":"Dominika Siodłak, Urszula Doboszewska, Gabriel Nowak, Piotr Wlaź, Katarzyna Mlyniec","doi":"10.1007/s00213-024-06736-0","DOIUrl":"https://doi.org/10.1007/s00213-024-06736-0","url":null,"abstract":"<p><strong>Rationale: </strong>Chronic stress is one of the leading causes of depression. Yet, knowledge of the pathomechanism of this process still eludes us. Chronic unpredictable mild stress (CUMS) model of depression enables researchers to look for a root cause of the disease in mice by mimicking a stressful human environment.</p><p><strong>Objective: </strong>Since zinc has already been shown to impact the treatment of depression, in our study we aimed to shed light on the role of the zinc receptor GPR39 in stress-induced depression. We also aimed to highlight the role of GPR39 activation in monoamine-based antidepressant treatment.</p><p><strong>Methods: </strong>Using large battery of behavioural tests, we provided a detailed description of CUMS-induced phenotype in both - CD-1 and GPR39 knock-out mice.</p><p><strong>Results: </strong>Our experiments showed that combined treatment with TC-G 1008 (GPR39 agonist) and antidepressants produces stronger antidepressant-like effect of classic antidepressants. We also demonstrated the inter-strain differences in stress response and the greater stress susceptibility of GPR39 knock-out mice. The lack of GPR39 expression also either diminished or completely abolished the response to treatment with different antidepressants combined with TC-G 1008.</p><p><strong>Conclusions: </strong>The results show that GPR39 KO mice are more susceptible to chronic stress and that they are non-responsive to SSRI treatment. Utilizing various behavioural tests gave us much broader understanding not only of the role of GPR39 in depression treatment, but also of the importance of detailed behavioural description in a proper interpretation of the results. Further research with known selective agonists and antagonists of GPR39 will be necessary to understand the full potential of this receptor as a pharmacological target.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953968","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":"Moderating factors in psilocybin-assisted treatment affecting mood and personality: A naturalistic, open-label investigation.","authors":"Mona Irrmischer, Drew Puxty, Barış Onur Yıldırım, Jan Berend Deijen, Hessel Engelbregt","doi":"10.1007/s00213-024-06733-3","DOIUrl":"https://doi.org/10.1007/s00213-024-06733-3","url":null,"abstract":"<p><strong>Rationale: </strong>Psychedelic-assisted therapy is increasingly applied within mental health treatment.</p><p><strong>Objectives: </strong>This study focused on factors moderating changes in the acute and long-term effects of an individual psilocybin-assisted program on depression, anxiety, PTSD and personality structures by including demographic factors, subjective experience and degree of mystical type experiences during the dosing, as well as emotional breakthrough and personal growth after the program.</p><p><strong>Methods: </strong>At baseline, 1 week and 3 months after the psilocybin program participants completed the Generalized Anxiety Disorder Assessment (GAD-7), Patient Health Questionnaire (PHQ-9), PTSD Checklist for DSM-5 (PCL-5) and NEO Five-Factor Inventory-3 (NEO-FFI-3). In addition, after the dosing the Mystical Experiences Questionnaire (MEQ-30), Posttraumatic Growth Inventory (PTGI) and Emotional Breakthrough Inventory (EBI) were administered. Moderation effects were established using linear mixed-model analysis.</p><p><strong>Results: </strong>A single high dose of psilocybin in combination with therapy was found to lower symptoms of anxiety, depression, PTSD and neuroticism over a period of 3-months. Scores on openness and conscientiousness increased after the treatment only. Participants reported mystical type experiences, emotional breakthrough and personal growth. These subjective experiences together with demographic factors were moderating the observed positive changes.</p><p><strong>Conclusions: </strong>Findings indicate that individual psilocybin-assisted therapy has the potential for beneficial effects on mood and personality characteristics. Moreover, the study highlights the importance of subjective experiences and demographic factors in moderating this effect. This study adds to the ongoing research on psilocybin-assisted therapy by investigating contributing factors for optimizing this evolving type of therapy.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953969","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 (CBD) potentiates physiological and behavioral markers of hypothalamic-pituitary-adrenal (HPA) axis responsivity in female and male mice.","authors":"Bryan W Jenkins, Hayley A Spina, Kate Nicholson, Amy E M Newman, Jibran Y Khokhar","doi":"10.1007/s00213-024-06737-z","DOIUrl":"https://doi.org/10.1007/s00213-024-06737-z","url":null,"abstract":"<p><strong>Rationale: </strong>Clinical literature indicates there may be a therapeutic use of cannabidiol (CBD) for stress-related disorders. Preclinical literature remains conflicted regarding the underlying neurobehavioral mechanisms, reporting mixed effects of CBD (increased, decreased, or no effect) on anxiety- and fear-related behaviors. Preclinical data demonstrated that CBD modulates hypothalamus-pituitary-adrenal (HPA) axis gene expression; it is unknown whether CBD changes HPA axis responsivity and how this relates to altered behavior.</p><p><strong>Objectives: </strong>We aimed to evaluate whether acute or chronic CBD administration would alter physiological and behavioral measures of HPA axis responsivity in male or female mice.</p><p><strong>Methods: </strong>C57BL/6 mice of both sexes were injected with vehicle or CBD (30 mg/kg, i.p.) daily for 26 days. Plasma corticosterone (CORT) levels were evaluated following dexamethasone suppression and adrenocorticotropin hormone stimulation tests after acute and chronic CBD exposure. After chronic CBD, mice were tested for anxiety-like behavior using an elevated plus maze (EPM) and associative fear learning and memory using a trace fear conditioning (FC) protocol.</p><p><strong>Results: </strong>Compared to vehicle, CBD induced a state of HPA axis hyperactivation, an effect which was significant in males; it also normalized anxiety-like behavior in female mice classified as having HPA axis hypofunction and primed all female mice for enhanced conditioned responding. Significant sex differences were also detected: females had greater plasma CORT levels and HPA axis responsivity than males, exhibited less EPM anxiety-like behavior, and were more responsive during FC.</p><p><strong>Conclusions: </strong>CBD potentiated physiological and behavioral markers of HPA axis function and normalized anxiety-like behavior in a sex-specific manner. This observation has implications for cannabinoid-based drug development targeting individuals with stress-related disorders involving HPA axis hypofunction pathology.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927960","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":"Practical considerations in the establishment of psychedelic research programs.","authors":"Brian S Barnett, M Frances Vest, Marcus S Delatte, Franklin King Iv, Erin E Mauney, Anthony J Coulson, Sandeep M Nayak, Peter S Hendricks, George R Greer, Kevin S Murnane","doi":"10.1007/s00213-024-06722-6","DOIUrl":"10.1007/s00213-024-06722-6","url":null,"abstract":"<p><strong>Rationale: </strong>There is increasing interest in establishing psychedelic research programs at academic medical centers. However, psychedelics are intensely psychoactive, carry considerable sociopolitical baggage, and most are Schedule I drugs, creating significant potential impediments to implementation. There is little formal guidance for investigators on navigating the complex on-the-ground obstacles associated with establishing psychedelic research programs.</p><p><strong>Objectives: </strong>This article provides recommendations that may be helpful to investigators seeking to work with psychedelics, with a focus on academic medical centers in the United States.</p><p><strong>Methods: </strong>The academic literature on relevant matters is reviewed, and the authors provide observations from their experiences either working for relevant regulatory agencies or conducting basic science studies, investigator-initiated trials, or industry sponsored trials with psychedelics.</p><p><strong>Results: </strong>Investigators planning to conduct psychedelic research should cultivate broad institutional support early. Challenges related to securing funding, obtaining approval for an Investigational New Drug application from the Food and Drug Administration, clinical grade drug sourcing, obtaining a Schedule I researcher registration from the Drug Enforcement Administration and an equivalent state license (if required), preparing spaces for treatment and study drug storage, managing controlled substance inventory, engaging the local community, and other issues should be anticipated.</p><p><strong>Conclusions: </strong>Investigators should anticipate several implementation challenges when planning to work with psychedelics. However, these are likely surmountable with planning, persistence, and assistance from colleagues and other experts.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"27-43"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771632","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":"Safety and efficacy of dasotraline for patients with attention deficit/hyperactivity disorder: a systematic review and meta-analysis of 1594 patients including GRADE qualifications.","authors":"Mohamed Ezzat M Mansour, Khalid Radwan Alsaadany, Mohamed Awad E Ahmed, Ahmed Ezzat Elmetwalli","doi":"10.1007/s00213-024-06723-5","DOIUrl":"10.1007/s00213-024-06723-5","url":null,"abstract":"<p><strong>Introduction: </strong>Attention-deficit/hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder. It is one of the most common mental disorders in youth worldwide characterized by persistent overactivity and impulsivity/inattention symptoms associated with social and academic impairment. dasotraline has been suggested to play a pivotal role as a serotonin, norepinephrine, and dopamine reuptake inhibitor. This study aimed to create evidence from published randomized clinical trials (RCTs) about the benefits of dasotraline for ADHD patients.</p><p><strong>Methods: </strong>A computer literature search (PubMed, Scopus, Web of Science, and Cochrane CENTRAL) was conducted. We included RCTs comparing dasotraline versus placebo. The primary outcome measure was the ADHD Rating Scale-IV score, pooled as the mean difference between the two groups from baseline to the endpoint. The secondary outcome measures were the ADHD Rating Scale-IV Inattention score, ADHD Rating Scale-IV Hyperactivity score.</p><p><strong>Results: </strong>Five RCTs with a total of 1594 patients were included in this study. dasotraline showed a significant improvement in the primary outcome (MD -2.65, 95% CI [-4.14 to -1.17], P= 0.0004 CONCLUSION: The results showed that dasotraline demonstrated a significant improvement in both primary and secondary outcomes, establishing its efficacy as a novel treatment for ADHD symptoms. However, mild to moderate side effects were observed.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"45-62"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865321","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":"Isobutyryl-carfentanyl has strong acute toxicity and analgesic effects with high addiction potential.","authors":"Deli Xu, Lixin Kuai, Yuanyuan Chen, Xianbin Zeng, Dan Wang, Bin Di, Peng Xu","doi":"10.1007/s00213-024-06664-z","DOIUrl":"10.1007/s00213-024-06664-z","url":null,"abstract":"<p><strong>Rationale: </strong>Isobutyryl-carfentanyl is the most recently discovered fentanyl analogue with a chemical structure that is similar to that of carfentanyl. Its analogue, carfentanyl, is regarded as one of the most lethal drugs in the world, with a potency of 10,000 times that of morphine. Therefore, isobutyryl-carfentanyl may possess a comparably high potency and its harmful effects cannot be ignored.</p><p><strong>Objectives: </strong>This study was designed to assess the analgesic effect of isobutyryl-carfentanyl and the potential risks associated with its misuse.</p><p><strong>Methods: </strong>In this study, we assessed the acute toxicity of isobutyryl-carfentanyl by up-and-down-procedure, the analgesic efficacy by hot-plate test, the abuse potential by conditioned place preference (CPP), drug self-administration, and drug discrimination tests, and compared it with fentanyl and carfentanyl.</p><p><strong>Results: </strong>The estimated median lethal dose (LD₅₀) of isobutyryl-carfentanyl administered were 175 mg/kg (intragastric administration, IG), 15.84 mg/kg (intraperitoneal injection, IP), 15.84 mg/kg (subcutaneous injection, SC), and 1.6 mg/kg (intravenous injection, IV), respectively. The 50% maximal analgesic effect (ED₅₀) of isobutyryl-carfentanyl was determined to be 0.00319 mg/kg, with an analgesic potency 14 times that of fentanyl and 0.82 times that of carfentanyl. Isobutyryl-carfentanyl exhibited a significant positional preference at a minimum dose of 0.1 mg/kg, while fentanyl exhibited a significant positional preference at a minimum dose of 0.3 mg/kg. In the heroin (0.05 mg/kg/infusion) self-administration substitution experiment, isobutyryl-carfentanyl showed significant self-administration behaviour at doses of 0.0005-0.001 mg/kg/infusion, with the maximum number of infusions observed at a dose of 0.001 mg/kg. In the heroin (1 mg/kg) drug discrimination experiment, fentanyl (0.005-0.02 mg/kg), carfentanyl (0.0005-0.002 mg/kg), and isobutyryl-carfentanyl (0.001-0.005 mg/kg) were tested in the dose-effect curves. The results showed that all three drugs exhibit dose-dependent increase in the number of drug-associated nose pokes responses and reduction in the rate of nose pokes. The subjective effect potency of isobutyryl-carfentanyl was found to be 4.4 times that of fentanyl and 0.5 times that of carfentanyl.</p><p><strong>Conclusions: </strong>In summary, isobutyryl-carfentanyl has high acute toxicity and analgesic effect, with strong psychological dependence approximately 5 times that of fentanyl and 0.5 times that of carfentanyl, and has extremely high abuse potency.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"205-214"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141898061","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":"Late development of OCD-like phenotypes in Dlgap1 knockout mice.","authors":"Kimino Minagawa, Takashi Hayakawa, Hayato Akimoto, Takuya Nagashima, Yasuo Takahashi, Satoshi Asai","doi":"10.1007/s00213-024-06668-9","DOIUrl":"10.1007/s00213-024-06668-9","url":null,"abstract":"<p><strong>Rationale: </strong>Despite variants in the Dlgap1 gene having the two lowest p-value in a genome-wide association study of obsessive compulsive disorder (OCD), previous studies reported the absence of OCD-like phenotypes in Dlgap1 knockout (KO) mice. Since these studies observed behavioral phenotypes only for a short period, development of OCD-like phenotypes in these mice at older ages was still plausible.</p><p><strong>Objective: </strong>To examine the presence or absence of development of OCD-like phenotypes in Dlgap1 KO mice and their responsiveness to fluvoxamine.</p><p><strong>Methods and results: </strong>Newly produced Dlgap1 KO mice were observed for a year. Modified SHIRPA primary screen in 2-month-old homozygous mutant mice showed only weak signs of anxiety, stress conditions and aggression. At older ages, however, these mutant mice exhibited excessive self-grooming characterized by increased scratching which led to skin lesions. A significant sex difference was observed in this scratching behavior. The penetrance of skin lesions reached 50% at 6-7 months of age and 90% at 12 months of age. In the open-field test performed just after the appearance of these lesions, homozygous mutant mice spent significantly less time in the center, an anxiety-like behavior, than did their wild-type and heterozygous littermates, none and less than 10% of which showed skin lesions at 1 year, respectively. The skin lesions and excessive self-grooming were significantly alleviated by two-week treatment with fluvoxamine.</p><p><strong>Conclusion: </strong>Usefulness of Dlgap1 KO mice as a tool for investigating the pathogenesis of OCD-like phenotypes and its translational relevance was suggested.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"215-231"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036770","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}