Psychopharmacology最新文献

{"title":"Acute and chronic cannabis vapor exposure produces immediate and delayed impacts on phases of fear learning in a sex specific manner.","authors":"Savannah H M Lightfoot, Andrei S Nastase, Gabriela Costa Lenz Cesar, Catherine Hume, Renaud C Gom, G Campbell Teskey, Matthew N Hill","doi":"10.1007/s00213-025-06748-4","DOIUrl":"https://doi.org/10.1007/s00213-025-06748-4","url":null,"abstract":"<p><strong>Rationale: </strong>Current treatment options for PTSD have unreliable efficacy, with many individuals unable to achieve complete remission. Cannabis and cannabinoids that act through the endogenous cannabinoid (endocannabinoid) system to help promote trauma recovery by means of enhanced extinction learning are potential therapeutic, pharmacological candidates. Using a preclinical model of translationally-relevant cannabis administration in rodents, we examined the impact of cannabis exposure on aversive memory.</p><p><strong>Objectives: </strong>Our study investigated the effects of acute cannabis exposure prior to (1) fear conditioning and (2) fear extinction, as well as (3) chronic cannabis exposure prior to fear conditioning, on the behavioural representations of fear memory dynamics in a Pavlovian auditory conditioning paradigm.</p><p><strong>Methods: </strong>Male and female Sprague Dawley rats were acutely or chronically exposed to THC-dominant cannabis extract or vehicle vapor as described above. We then assessed both passive (freezing) and active (darting) fear behaviours during conditioning, extinction, retrieval, and spontaneous recovery.</p><p><strong>Results: </strong>Acute cannabis exposure prior to conditioning had no immediate effects on fear acquisition, but impaired fear recall in females 24 h later and prevented spontaneous recovery of conditioned fear following a two-week retrieval test in both male and female rats. Acute cannabis exposure prior to extinction training impaired extinction in females while enhancing extinction acquisition in males. Finally, chronic THC exposure prior to fear conditioning initially potentiated fear responses, predominately in females, but produced no differences in spontaneous recovery in a two-week retrieval test.</p><p><strong>Conclusions: </strong>Cannabis exposure has complex dynamics on fear memory, however, acute cannabis exposure prior to fear learning appears to result in destabilization of the fear memory long term, which could have potential implications for PTSD.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067620","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":"Neural cue reactivity and intrinsic functional connectivity in individuals with alcohol use disorder following treatment with topiramate or naltrexone.","authors":"Warren B Logge, Paul S Haber, Tristan Hurzeler, Hugh Gallagher, Henry Kranzler, Kirsten C Morley","doi":"10.1007/s00213-025-06745-7","DOIUrl":"https://doi.org/10.1007/s00213-025-06745-7","url":null,"abstract":"<p><strong>Rationale: </strong>Both topiramate and naltrexone have been shown to affect neural alcohol cue reactivity in alcohol use disorder (AUD). However, their comparative effects on alcohol cue reactivity are unknown. Moreover, while naltrexone has been found to normalize hyperactive localized network connectivity implicated in AUD, no studies have examined the effect of topiramate on intrinsic functional connectivity or compared functional connectivity between these two widely used medications.</p><p><strong>Objective: </strong>This study compared topiramate versus naltrexone on alcohol cue-elicited brain activation and intrinsic functional connectivity in patients with alcohol use disorder.</p><p><strong>Methods: </strong>Forty-seven participants with alcohol use disorder received daily topiramate (titrating the dose up to 200 mg/day n = 21) or naltrexone (50 mg/day, n = 26) for at least 6 weeks. Using functional magnetic resonance imaging (fMRI), we examined intrinsic functional connectivity during rest and alcohol cue-elicited neural activation during a visual alcohol cue reactivity task 120 min following treatment administration. Functional connectivity and alcohol cue reactivity and percentage of heavy drinking days (% HDD) associations were assessed.</p><p><strong>Results: </strong>No differences in either intrinsic functional connectivity or alcohol cue-elicited neural activity were seen between topiramate and naltrexone-treated groups. Overall, participants showed increased alcohol cue-elicited activation in three clusters spanning occipital regions involved in visual recognition of stimuli, and hypoactivation to both alcohol and control cues in three clusters involved in salience attribution and processing of emotional valence of external stimuli. No differences between topiramate versus naltrexone were observed for either functional measure or associations with post-scan % HDD.</p><p><strong>Conclusions: </strong>Topiramate and naltrexone enacted comparable alcohol cue reactivity and intrinsic functional connectivity patterns. Some overall responses of increased brain activation to alcohol cues in visual processing regions coupled with reduced activation to alcohol and control cues were evidenced for both treatments. These activation patterns were in regions expected to show attenuation of brain activity resulting from treatment. Topiramate and naltrexone may thus enact functional effects through similar modulation of functional neural activity in individuals with AUD.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT03479086 https://www.</p><p><strong>Clinicaltrials: </strong>gov/study/NCT03479086 .</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033971","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":"Acute effects of psilocybin on attention and executive functioning in healthy volunteers: a systematic review and multilevel meta-analysis.","authors":"P Yousefi, Morten P Lietz, F J O'Higgins, R C A Rippe, G Hasler, M van Elk, S Enriquez-Geppert","doi":"10.1007/s00213-024-06742-2","DOIUrl":"10.1007/s00213-024-06742-2","url":null,"abstract":"<p><strong>Rationale: </strong>Psilocybin shows promise for treating neuropsychiatric disorders. However, insight into its acute effects on cognition is lacking. Given the significant role of executive functions in daily life and treatment efficacy, it is crucial to evaluate how psilocybin influences these cognitive domains.</p><p><strong>Objectives: </strong>This meta-analysis aims to quantify the acute effects of psilocybin on executive functions and attention, while examining how dosage, timing of administration, cognitive domain, and task characteristics moderate these effects.</p><p><strong>Methods: </strong>A systematic review and multilevel meta-analysis were conducted on empirical studies assessing psilocybin's acute effects on working memory, conflict monitoring, response inhibition, cognitive flexibility, and attention. Effect sizes for reaction time (RT) and accuracy (ACC) were calculated, exploring the effects of timing (on-peak defined as 90-180 min post-administration), dosage, cognitive function categories, and task sensitivity to executive functions as potential moderators.</p><p><strong>Results: </strong>Thirteen studies (42 effect sizes) were included. In the acute phase, psilocybin increased RTs (Hedges' g = 1.13, 95% CI [0.57, 1.7]) and did not affect ACC (Hedges' g = -0.45, 95% CI [-0.93, 0.034]). Effects on RT were dose dependent. Significant between-study heterogeneity was found for both RT and ACC. Task sensitivity to executive functions moderated RT effects. Publication bias was evident, but the overall effect remained significant after adjustment for this.</p><p><strong>Conclusions: </strong>Our meta-analysis shows that psilocybin impairs executive functions and results in a slowing down of RT. We discuss potential neurochemical mechanisms underlying the observed effects as well as implications for the safe use of psilocybin in clinical and experimental contexts.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024461","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":"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":"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}

{"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":"Interactions of pain and opioids on conditioned place preference in rodents.","authors":"Angela E Barattini, Amanda R Pahng","doi":"10.1007/s00213-024-06719-1","DOIUrl":"10.1007/s00213-024-06719-1","url":null,"abstract":"<p><strong>Rationale: </strong>Opioid analgesics are the most effective medications used for the treatment of pain, however there are significant risks associated with repeated opioid use including opioid misuse and opioid use disorder development. Chronic pain affects millions of adults in the United States, and opioid misuse is often comorbid with pain conditions in individuals who are repeatedly treated with opioids. In addition to providing pain relief, opioids produce rewarding effects, but in chronic pain states, reward processing can become dysregulated. The conditioned place preference task is commonly used to measure the rewarding properties of opioids in rodents. During this task, opioid administration is paired with a distinct environment through repeated conditioning and the change in an animal's preference for the paired environment indicates whether the opioid is rewarding or not.</p><p><strong>Objectives: </strong>Rodent pain models can be combined with conditioned place preference to examine the effects of pain on opioid reward. The existing preclinical literature on pain effects on conditioned place preference is conflicting, where pain conditions have been reported to enhance, suppress, or have no effect on opioid reward. This review will discuss several factors that may contribute to these discordant findings including conditioning session duration and number, rodent strain differences in opioid sensitivity, analgesic properties of opioids at tested doses, locomotor effects at tested doses, and diurnal variation in pain sensitivity. Future studies should consider how these factors contribute to opioid conditioned place preference in both pain and pain-free animals to have a better understanding of the interactions between pain and opioid reward.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"1-26"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676774","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}