Psychopharmacology最新文献

{"title":"Efficacy of agomelatine on sleep disorders and lateral habenula neuronal activity in chronic restraint stress depression model mice.","authors":"Zhuojun Kang, Zhenzhen Zheng, Wenli Guo","doi":"10.1007/s00213-024-06681-y","DOIUrl":"10.1007/s00213-024-06681-y","url":null,"abstract":"<p><strong>Background: </strong>Sleep disorders (SD) are one of the common manifestations of depression patients. This article aimed to explore the effect of Agomelatine (Ago) on SD in chronic restraint stress (CRS) depression model mice and its effect on the activity of neurons in the lateral habenula (LHb).</p><p><strong>Methods: </strong>30 C57BL/6 J mice were divided into normal (C57BL/6 J) group, CRS group, and Ago group. CRS experiment was used to establish the depression model, and Ago was used to treat CRS mice. Based on behavioral tests in mice and electrophysiology record, SD and LHb neuron activity were assessed. The expression levels of brain-derived neurotrophic factor (BDNF) and nuclear phosphoprotein (c-Fos) in LHb were detected by Western blot (WB).</p><p><strong>Results: </strong>As against the CRS group, the Ago group had a reduction in the immobility time during forced swimming training and an increase in the preference for sucrose in the sucrose preference test; The expression levels of c-Fos and BDNF proteins in the LHb neurons of the Ago group mice were lower than those in the CRS group (P < 0.05), and the values approached the levels of the normal control group. In both dark and light environments, the rapid eye movement (REM) sleep duration of the CRS group mice was significantly longer than that of the normal control group (P < 0.05).</p><p><strong>Conclusion: </strong>It was concluded that Ago may intervene in the depressive-like behavior and overall sleep patterns of CRS depression model mice by regulating the activity of LHb neurons and inhibiting the neuroinflammatory process. This provides a potential drug target for the development of new treatment strategies for depression.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"353-360"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154819","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":"The ultrasonic vocalization (USV) syllable profile during neonatal opioid withdrawal and a kappa opioid receptor component to increased USV emissions in female mice.","authors":"Kelly K Wingfield, Teodora Misic, Kaahini Jain, Carly S McDermott, Nalia M Abney, Kayla T Richardson, Mia B Rubman, Jacob A Beierle, Sophia A Miracle, Emma J Sandago, Britahny M Baskin, William B Lynch, Kristyn N Borrelli, Emily J Yao, Elisha M Wachman, Camron D Bryant","doi":"10.1007/s00213-024-06694-7","DOIUrl":"10.1007/s00213-024-06694-7","url":null,"abstract":"<p><strong>Rationale: </strong>Opioid use during pregnancy can lead to negative infant health outcomes, including neonatal opioid withdrawal syndrome (NOWS). NOWS comprises gastrointestinal, autonomic nervous system, and neurological dysfunction that manifest during spontaneous withdrawal. Variability in NOWS severity necessitates a more individualized treatment approach. Ultrasonic vocalizations (USVs) in neonatal mice are emitted in isolation as a stress response and are increased during opioid withdrawal, thus modeling a negative affective state that can be utilized to test new treatments.</p><p><strong>Objectives: </strong>We sought to identify the behavioral and USV profile, brainstem transcriptomic adaptations, and role of kappa opioid receptors in USVs during neonatal opioid withdrawal.</p><p><strong>Methods: </strong>We employed a third trimester-approximate opioid exposure model, where neonatal inbred FVB/NJ pups were injected twice-daily with morphine (10mg/kg, s.c.) or saline (0.9%, 20 ul/g, s.c.) from postnatal day(P) 1 to P14. This protocol induces reduced weight gain, hypothermia, thermal hyperalgesia, and increased USVs during spontaneous morphine withdrawal.</p><p><strong>Results: </strong>On P14, there were increased USV emissions and altered USV syllables during withdrawal, including an increase in Complex 3 syllables in FVB/NJ females (but not males). Brainstem bulk mRNA sequencing revealed an upregulation of the kappa opioid receptor (Oprk1), which contributes to withdrawal-induced dysphoria. The kappa opioid receptor (KOR) antagonist, nor-BNI (30 mg/kg, s.c.), significantly reduced USVs in FVB/NJ females, but not males during spontaneous morphine withdrawal. Furthermore, the KOR agonist, U50,488h (0.625 mg/kg, s.c.), was sufficient to increase USVs on P10 (both sexes) and P14 (females only) in FVB/NJ mice.</p><p><strong>Conclusions: </strong>We identified an elevated USV syllable, Complex 3, and a female-specific recruitment of the dynorphin/KOR system in increased USVs associated with neonatal opioid withdrawal severity.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"427-447"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352690","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":"The effect of nightly use of 150 mg cannabidiol on daytime neurocognitive performance in primary insomnia: a randomized controlled pilot trial.","authors":"Andrea J Narayan, Amie C Hayley, Sarah Rose, Lauren Di Natale, Luke A Downey","doi":"10.1007/s00213-024-06674-x","DOIUrl":"10.1007/s00213-024-06674-x","url":null,"abstract":"<p><strong>Rationale: </strong>Cannabidiol (CBD) is increasingly used as a sleep aid for insomnia; yet neurocognitive and subjective state effects following daily therapeutic use are unclear.</p><p><strong>Objectives: </strong>To measure the effect of daily CBD use on neurocognitive performance and daily subjective mood in a population with primary insomnia.</p><p><strong>Methods: </strong>This study used a randomized, placebo-controlled, parallel design incorporating a single-blind placebo run-in week followed by a two-week double-blind dosing period, during which participants consumed 150 mg CBD (N = 15) or placebo (N = 15) sublingually 60-minutes daily before bed. Attention, executive function, reasoning, information processing, working and episodic memory were assessed using the CogPro system at the beginning of the placebo run-in, after 1-week and 2-weeks of dosing. Subjective states using visual analogue scales and side effects were recorded daily.</p><p><strong>Results: </strong>Cognitive performance was unaffected by nightly CBD supplementation (all p > 0.05). From baseline to trial conclusion, those receiving CBD reported greater experience of calmness, clear-headedness, coordination and were more likely to report side-effects of dry mouth relative to placebo (all p < 0.05).</p><p><strong>Conclusions: </strong>Relative to placebo, daytime cognitive functioning following nightly supplementation as a therapeutic aid for primary insomnia was preserved under trial conditions. Results suggested an overall favourable safety profile, with larger controlled trials and thorough analyses of varying insomnia phenotypes necessary to corroborate these findings.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"297-308"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996335","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":"Acute analgesic effect of nicotine vaping using three experimental pain induction tasks: a randomized, placebo-controlled laboratory study.","authors":"Michael P Bremmer, Michael B Paladino, Alana M Campbell, Kai Xia, Robert Tarran, Christian S Hendershot, Susan S Girdler","doi":"10.1007/s00213-024-06669-8","DOIUrl":"10.1007/s00213-024-06669-8","url":null,"abstract":"<p><strong>Rationale: </strong>Pain and nicotine use are co-occurring conditions with a significant impact on health. Experimental evidence supports an acute analgesic effect of nicotine which may reinforce nicotine use among those with chronic pain. Evidence for nicotine analgesia have primarily been gathered in combustible cigarette users and have not been extended to electronic nicotine delivery systems (ENDS or vaping). Furthermore, the mechanisms of nicotine analgesia in humans are not well understood.</p><p><strong>Objectives: </strong>Assess the effect of acute vaped nicotine on subjective and behavioral indices of pain sensitivity using three tasks designed to probe distinct mechanisms of analgesia.</p><p><strong>Methods: </strong>This study recruited ENDS users (N = 86) to undergo a paced vaping protocol followed by pain tasks in counterbalanced order. Across four sessions, participants vaped e-liquid containing nicotine or placebo, and flavor or no-flavor in a 2 × 2 within-subject design. Assessments included cold pressor, submaximal effort tourniquet to induce ischemic pain, and temporal summation of heat pain, an index of central sensitization.</p><p><strong>Results: </strong>Compared to placebo, nicotine increased cold pressor pain tolerance (η_p² = 0.031), ischemic pain threshold (η_p² = 0.073) and tolerance (η_p² = 0.056) but had no effect on temporal summation of pain. Flavor did not affect pain sensitivity. Females reported greater ischemic pain sensitivity (η_p² = 0.027) and greater reductions in craving (η_p² = 0.086).</p><p><strong>Conclusions: </strong>Consistent with research from tobacco smoking, analgesia may be reinforcing and contribute to nicotine dependence among ENDS users. More research on sex differences is warranted.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"235-245"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907579","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":"Effects of lorazepam on saccadic eye movements - evidence from prosaccade and free viewing tasks.","authors":"Philine M Baumert, Kaja Faßbender, Maximilian W M Wintergerst, Jan H Terheyden, Behrem Aslan, Tom Foulsham, Wolf Harmening, Ulrich Ettinger","doi":"10.1007/s00213-024-06672-z","DOIUrl":"10.1007/s00213-024-06672-z","url":null,"abstract":"<p><strong>Rationale: </strong>Peak velocities of saccadic eye movements are reduced after benzodiazepine administration. Even though this is an established effect, past research has only examined it in horizontal prosaccade tasks.</p><p><strong>Objectives: </strong>The spectrum of saccadic eye movements, however, is much larger. Therefore, we aimed to make a first attempt at filling this research gap by testing benzodiazepine effects on saccades under different experimental task conditions.</p><p><strong>Methods: </strong>1 mg lorazepam or placebo was administered (within-subjects, double-blind, in randomised order) to n = 30 healthy adults. Participants performed an extended version of the prosaccade task, including vertical saccade directions and different stimulus eccentricities, as well as a free viewing task.</p><p><strong>Results: </strong>Results from the prosaccade task confirmed established effects of benzodiazepines as well as saccade direction on saccadic parameters but additionally showed that the drug effect on peak velocity was independent of saccade direction. Remarkably, in the free viewing task peak velocities as well as other saccade parameters were unaffected by lorazepam. Furthermore, exploration patterns during free viewing did not change under lorazepam.</p><p><strong>Conclusions: </strong>Overall, our findings further consolidate the peak velocity of prosaccades as a biomarker of sedation. Additionally, we suggest that sedative effects of low doses of benzodiazepines may be compensated in tasks that more closely resemble natural eye movement behaviour, possibly due to the lack of time constraints or via neurophysiological processes related to volition.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"271-284"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120398","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":"Cannabidiol enhances socially transmitted food preference: a role of acetylcholine in the mouse basal forebrain.","authors":"Chih-Yu Chang, Wen Dai, Sherry Shu-Jung Hu","doi":"10.1007/s00213-024-06670-1","DOIUrl":"10.1007/s00213-024-06670-1","url":null,"abstract":"<p><strong>Rationale and objective: </strong>Rodents acquire food information from their conspecifics and display a preference for the conspecifics' consumed food. This social learning of food information from others promotes the survival of a species, and it is introduced as the socially transmitted food preference (STFP) task. The cholinergic system in the basal forebrain plays a role in the acquisition of STFP. Cannabidiol (CBD), one of the most abundant phytocannabinoids, exerts its therapeutic potential for cognitive deficits through versatile mechanisms of action, including its interaction with the cholinergic system. We hypothesize a positive relationship between CBD and STFP because acetylcholine (ACh) is involved in STFP, and CBD increases the ACh levels in the basal forebrain.</p><p><strong>Materials and methods: </strong>Male C57BL/6J mice were trained to acquire the STFP task. We examined whether CBD affects STFP memory by administering CBD (20 mg/kg, i.p.) before the STFP social training. The involvement of cholinergic system in CBD's effect on STFP was examined by knockdown of brain acetylcholinesterase (AChE), applying a nonselective muscarinic antagonist SCO (3 mg/kg, i.p.) before CBD treatment, and measuring the basal forebrain ACh levels in the CBD-treated mice.</p><p><strong>Results: </strong>We first showed that CBD enhanced STFP memory. Knockdown of brain AChE also enhanced STFP memory, which mimicked CBD's effect on STFP. SCO blocked CBD's memory-enhancing effect on STFP. Our most significant finding is that the basal forebrain ACh levels in the CBD-treated mice, but not their control counterparts, were positively correlated with mice's STFP memory performance.</p><p><strong>Conclusion: </strong>This study indicates that CBD enhances STFP memory in mice. Specifically, those which respond to CBD by increasing the muscarinic-mediated ACh signaling perform better in their STFP memory.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"247-269"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000598","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 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":"https://doi.org/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":"D₁ dopamine / mu opioid receptor interactions in operant conditioning assays of pain-depressed responding and drug-induced rate suppression, and a conditioned place preference procedure: assessment of therapeutic index in male Sprague Dawley rats.","authors":"Hannah LaCourse, Lily Bennett, April Falstad, Francesca Asmus, Meghan Smith, Ravin Davis, Kylee Harrington, Denise Giuvelis, Tamara King, Glenn W Stevenson","doi":"10.1007/s00213-025-06743-9","DOIUrl":"https://doi.org/10.1007/s00213-025-06743-9","url":null,"abstract":"<p><strong>Rationale and objectives: </strong>In vivo receptor interactions vary as a function of behavioral endpoint, with key differences between reflexive and non-reflexive measures that assess the motivational aspects of pain and pain relief. There have been no assessments of D₁ dopamine agonist / mu opioid receptor (MOR) agonist interactions in non-reflexive behavioral measures of pain. We examined the hypothesis that D₁/MOR mixtures show enhanced effectiveness in blocking pain depressed behaviors while showing decreased side effects such as sedation and drug reward.</p><p><strong>Methods: </strong>SKF82958 and methadone were used as selective/high efficacy D₁ and mu agonists, respectively. An FR10 operant schedule was utilized in the presence and absence of a lactic acid inflammatory pain-like manipulation, to measure antinociceptive and operant-rate-suppressing effects, respectively. Rewarding properties of the drug combinations were determined using a conditioned place preference procedure.</p><p><strong>Results: </strong>Methadone alone, but not SKF82958 alone, produced dose-dependent restoration of pain-depressed responding. Both SKF82958 and methadone produced dose-dependent response rate suppression. Three fixed proportion mixtures, based on the relative potencies of the drugs in the rate suppression assay, produced dose-dependent antinociception and sedation. Isobolographic analysis indicated that the 0.17:1 mixture produced supra-additive antinociception and additive sedation. The 0.055:1 mixture produced additive antinociception with sub-additive sedation, and the 0.018:1 mixture had the highest therapeutic index (TI) relative to other mixtures and drugs alone. The antinociceptive doses and component doses for the 0.018:1 mixture did not produce conditioned place preference.</p><p><strong>Conclusions: </strong>These results suggest that D₁-selective dopamine agonists may have utility as candidate opioid-sparing analgesics.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010587","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}