Psychopharmacology最新文献

{"title":"Correction to: Infuence of real-world cue exposure and mood states on drinking: testing neurobiological models of alcohol use disorder.","authors":"Lindsay R Meredith, Wave-Ananda Baskerville, Carrie Lee, Erica N Grodin, Kate M Wassum, Lara A Ray","doi":"10.1007/s00213-025-06769-z","DOIUrl":"10.1007/s00213-025-06769-z","url":null,"abstract":"","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543219","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 psychedelic (-)-2,5-dimethoxy-4-iodoamphetamine [(-)-DOI] demonstrates efficacy in reducing cocaine reward and motivation in male rats.","authors":"Leah M Salinsky, Christina R Merritt, Erik J Garcia, Robert G Fox, Joshua C Zamora, Noelle C Anastasio, Kathryn A Cunningham","doi":"10.1007/s00213-025-06765-3","DOIUrl":"https://doi.org/10.1007/s00213-025-06765-3","url":null,"abstract":"<p><strong>Rationale and objectives: </strong>Overdose fatalities involving cocaine continue to rise with over 5.3 million cocaine users reported in the United States in 2022. The abuse liability of cocaine is reliant upon inhibition of dopamine (DA) reuptake and consequent increase in DA efflux in meso-corticolimbic circuitry that controls reward and motivation. Cocaine also increases serotonin (5-HT) efflux which is integral in cocaine abuse. The 5-HT_2A receptor (5-HT_2AR) is a key regulator of meso-corticolimbic DA release and controls cellular mechanisms underlying cocaine effects. 5-HT_2AR actions contribute importantly to psychedelic mechanisms of action, and the efficacy of these compounds in limiting cocaine intake is unknown. The present studies evaluated the efficacy of acute administration of a psychedelic to reduce cocaine intake using standard and advanced preclinical models of drug self-administration.</p><p><strong>Methods: </strong>Both a standard fixed ratio (FR) schedule and behavioral economics threshold procedure of cocaine intravenous self-administration were employed to evaluate the efficacy of the psychedelic 5-HT_2AR agonist (-)-2,5-dimethoxy-4-iodoamphetamine [(-)-DOI] to decrease cocaine intake and motivation for cocaine in male rats. The 5-HT_2AR-selective antagonist M100907 was utilized to explore the role of 5-HT_2AR in the effects of (-)-DOI on cocaine intake.</p><p><strong>Results: </strong>We found that (-)-DOI dose-dependently reduced intake on the FR5 schedule of cocaine IVSA and left shifted the demand curve to evoke greater sensitivity to price increases in the behavioral economics paradigm. Pretreatment with M100907 abated the efficacy of (-)-DOI on cocaine intake in both paradigms.</p><p><strong>Conclusion: </strong>(-)-DOI 'devalued' cocaine reward and motivation to take cocaine in a 5-HT_2AR-dependent manner. As serotonergic psychedelics emerge as therapeutic candidates, investigations of 5-HT_2AR-acting psychedelics in preclinical analyses of cocaine intake and relapse vulnerability during abstinence will be valuable as prelude to future clinical trials.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543221","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":"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":"563-578"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861019/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol increases social engagement in dyadic interactions: role of partner's drug state.","authors":"Hanna Molla, Tyler O'Neill, Evan Hahn, Royce Lee, Harriet de Wit","doi":"10.1007/s00213-024-06714-6","DOIUrl":"10.1007/s00213-024-06714-6","url":null,"abstract":"<p><strong>Rationale: </strong>Alcohol is commonly used in social environments and is known to facilitate social behaviors. However, most controlled laboratory studies on alcohol have been conducted in isolated settings, limiting our understanding of its effects on social interactions.</p><p><strong>Objectives: </strong>The current study was designed to examine the effects of alcohol on dyadic interactions in healthy volunteers (N = 37), with a focus on the influence of the conversation partner's drug state.</p><p><strong>Methods: </strong>Using a 4-session, placebo-controlled, within-subjects design, participants received a moderate dose of alcohol (0.8 g/kg men) or placebo in randomized order before engaging in a 45-minute semi-structured conversation with a partner who received either alcohol or placebo. Partners were always strangers. Outcome measures included subjective responses to alcohol, self-reported closeness to partners, and facial expressions during interactions analyzed via a machine learning model.</p><p><strong>Results: </strong>Alcohol produced its expected subjective effects, some of which were enhanced when the partner also received alcohol. Alcohol enhanced enjoyment of social interactions and feelings of connectedness, irrespective of the partner's drug condition. Facial expression analysis revealed that alcohol increased positive and decreased negative emotional expressions. For women but not men, these effects were more pronounced when their conversation partners also received alcohol. Individual emotion analysis revealed that alcohol increased the intensity of facial expressions associated with amusement, joy, and excitement, while reducing emotions such as awkwardness and contempt.</p><p><strong>Conclusions: </strong>Our findings show that alcohol increases feelings of social connectedness, and that responses to alcohol can be influenced by the drug state of interacting partners. The increased feelings of social connection may contribute to risk for escalation of use.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"629-640"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865212","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":"Orexin mechanisms in the prelimbic cortex modulate the expression of contextual conditioned fear.","authors":"Gabriela V M Oliveira, Paloma M Hernandes, Fábio H Dos Santos, Victor P M N Soares, Luiz Luciano Falconi-Sobrinho, Norberto C Coimbra, Carsten T Wotjak, Rafael Carvalho Almada","doi":"10.1007/s00213-024-06701-x","DOIUrl":"10.1007/s00213-024-06701-x","url":null,"abstract":"<p><strong>Rationale: </strong>Despite the existing anatomical and physiological evidence pointing to the involvement of orexinergic projections from the lateral hypothalamus (LH) in regulating fear-related responses, little is known regarding the contribution of the orexin system in the prelimbic cortex (PL) on contextual fear.</p><p><strong>Objectives: </strong>We investigated the role of orexin-A (Orx_A) and orexin type 1 receptors (Orx₁R) in the PL during the expression of contextual conditioned fear in mice.</p><p><strong>Methods: </strong>Neural tract tracing of the LH-PL pathway and Orx₁R immunoreactivity in the PL of C57BL/6 male mice were performed. In a pharmacological approach, the animals were treated with either the Orx₁R selective antagonist SB 334,867 (3, 30, and 300 nM/0.1 µL) or Orx_A (28, 70, and 140 pmol/0.1 µL) in the PL before the test session of contextual fear conditioning.</p><p><strong>Results: </strong>Neural tract tracing deposits in the LH showed some perikarya, mainly axons and terminal buttons in the PL, suggesting LH-PL reciprocate pathways. Furthermore, we showed a profuse network comprised of Orx₁R-labeled thin varicose fibers widely distributed in the same field of LH-PL pathways projection. The selective blockade of Orx₁R with SB 334,867 at 30 and 300 nM in the PL caused a decrease in freezing response, whereas the treatment with Orx_A at 140 pmol promoted an increase in freezing response.</p><p><strong>Conclusion: </strong>In summary, these data confirmed an anatomical link between LH and PL, established the presence of Orx₁R in the PL, and a modulatory role of the orexin system in such structure, possibly mainly via Orx₁R, during contextual fear conditioning.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"521-532"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401090","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 effects of caffeine mouth rinsing on selective attention as a function of different caffeine concentrations and perceived taste intensity in recreationally active males at rest: a randomized placebo-controlled cross-over trial.","authors":"Cemile Balcı, Neşe Toktaş, Kemal Alparslan Erman, Abdurrahman Aktop, Ethem Kavukçu, Asuman Şahan","doi":"10.1007/s00213-024-06710-w","DOIUrl":"10.1007/s00213-024-06710-w","url":null,"abstract":"<p><strong>Rationale: </strong>The effect of caffeine mouth rinsing (CAF-MR) on cognitive performance has not been thoroughly investigated.</p><p><strong>Objectives: </strong>To evaluate the effects of different concentrations of CAF-MR on selective attention in relation to perceived taste intensity.</p><p><strong>Methods: </strong>A total of 30 healthy and recreationally active male subjects were included in this randomized, double-blind, placebo-controlled crossover trial. Interventions included MR for 20 s at rest with three different caffeine solutions (0.24% [60 mg/25 mL], 0.6% [150 mg/25 mL], and 1.2% [300 mg/25 mL]), MR with 25 mL water (placebo), and no MR (control). Data on Victoria Stroop Test (VST) and the perceived taste intensity were recorded at five sessions.</p><p><strong>Results: </strong>CAF-MR-300 mg intervention significantly decreased completion time (from 62.93 ± 19.07 to 57.01 ± 16.74 s, p = 0.002 in Part D), while CAF-MR-150 mg intervention significantly decreased number of errors in Part D (7.00 ± 6.21 vs. 5.63 ± 5.76, p = 0.04) and Part C (8.77 ± 8.80 vs. 7.10 ± 7.11, p = 0.02). Perceived difficulty was significantly decreased both after CAF-MR with 150 mg (5.57 ± 1.65 vs. 4.77 ± 1.98, p = 0.006) and 300 mg (5.95 ± 1.77vs. 4.67 ± 1.96, p < 0.001). Perceived taste intensity for 300 mg of caffeine was negatively correlated with completion time (r: ranged, 0.37 to 0.46, p ranged, 0.045 to 0.009) after 300 mg, 150 mg (p ranged, 0.04 to 0.005) and placebo (p ranged 0.044 to 0.03) interventions.</p><p><strong>Conclusions: </strong>This study is the first to demonstrate that CAF-MR shows dose-dependent effects on selective attention in healthy recreational males, such as improved speed (for 300 mg caffeine), reduced error rate (for 150 mg caffeine) and decrease in perceived difficulty (for 150 and 300 mg caffeine).</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"579-592"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568408","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 effect of mixed tobacco monoamine oxidase inhibitors in animal models relevant to tobacco dependence.","authors":"Penelope Truman, Diana Vivian Atigari, Meyrick Kidwell, Joyce Colussi-Mas, Bart Ellenbroek","doi":"10.1007/s00213-024-06712-8","DOIUrl":"10.1007/s00213-024-06712-8","url":null,"abstract":"<p><strong>Rationale: </strong>Tobacco monoamine oxidase (MAO) inhibitors have long been suspected of influencing tobacco dependence, but direct evidence of their effects has been difficult to obtain. Recently we have identified two new groups of monoamine oxidase inhibitors, hydroquinones and polyunsaturated fatty acids (linoleic and linolenic acid), abundant in tobacco smoke.</p><p><strong>Objectives: </strong>To test, in relevant animal models, whether the combined effect of these inhibitors is sufficient to affect addictive responses to nicotine.</p><p><strong>Methods: </strong>Here we report the first tests of the effects of mixed tobacco MAO inhibitors in three animal behavioural tests relevant to nicotine addiction, conditioned place preference, locomotor sensitisation and nicotine self-administration. Inhibitors used were the aforementioned linoleic and linolenic acid, and catechol, 4-ethylcatechol, 4-methyl catechol and hydroquinone, together with the already known inhibitors harman and norharman. They were administered together in the ratios found in tobacco smoke.</p><p><strong>Results: </strong>In conditioned place preference and in self-administration tests the addition of these tobacco MAO inhibitors significantly increased responding to nicotine and motivation to self-administer nicotine, supporting the hypothesis that inhibition of MAO enzymes in the brain enhances addictive responses such as that for nicotine. The combined MAO inhibitors without nicotine did not cause increased locomotor activity and did not induce a place conditioned response.</p><p><strong>Conclusions: </strong>Our results show that the combined effect of three groups of major MAO inhibitors present in tobacco smoke can enhance the addictive responses to nicotine in rats. There is no evidence from this study that these MAO inhibitors are addictive in themselves.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"617-628"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648787","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":"Ferulic acid ameliorates bisphenol A (BPA)-induced Alzheimer's disease-like pathology through Akt-ERK crosstalk pathway in male rats.","authors":"Mhasen Khalifa, Rabie H Fayed, Yasmine H Ahmed, Mohamed F Abdelhameed, Ahmed F Essa, Heba M A Khalil","doi":"10.1007/s00213-024-06697-4","DOIUrl":"10.1007/s00213-024-06697-4","url":null,"abstract":"<p><strong>Objectives: </strong>This study investigated the neuroprotective effect of ferulic acid (FA) against bisphenol A (BPA) induced Alzheimer's disease-like pathology in male rats.</p><p><strong>Methods: </strong>Rats were allocated into four groups, control, BPA, BPA + FA, and FA, respectively, for 40 days. Spatial working memory and recognition memory were evaluated. Moreover, the brain levels of oxidative stress biomarkers, proinflammatory cytokines, extracellular signal-regulated kinase (ERK), and phosphorylated serine/threonine protein kinase (p-Akt) were measured. We also determined the brain neuropathological protein levels, including Beta-Amyloid 1-42, total Tau (tTau), and phosphorylated Tau (pTau) proteins. Furthermore, brain levels of Acetylcholinesterase (AChE) and Beta-secretase (BACE) were assessed. Brain histological investigation and immunohistochemistry determination of glial fibrillar acidic protein (GFAP) were also performed. Moreover, docking simulation was adapted to understand the inhibitory role of FA on AChE, BACE-1, and ERK1/2.</p><p><strong>Results: </strong>Interestingly, the BPA + FA treated group showed a reversal in the cognitive impairments induced by BPA, which was associated with improved brain redox status. They also exhibited a significant decrease in brain inflammatory cytokines, ERK, and p-Akt levels. Moreover, they revealed a decline in beta-amyloid 1-42 and a significant improvement in tTau expression and pTau protein levels in the brain tissue. Further, the brain levels of AChE and BACE were substantially reduced in BPA + FA rats. The neuroprotective effect of FA was confirmed by restoring the normal architecture of brain tissue, which was associated with decreasing GFAP.</p><p><strong>Conclusion: </strong>FA could be a potent neuroprotectant agent against AD with a possible prospect for its therapeutic capabilities and nutritional supplement value due to its antioxidant and antiapoptotic properties.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"461-480"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506714","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":"Assessment of pharmacological effects and abuse potential of 5F-EDMB-PICA, CUMYL-PEGACLONE, and NM-2201 in mice.","authors":"Kaixi Li, Deli Xu, Yanling Qiao, Lixin Kuai, Xuwen Luo, Bin Di, Peng Xu","doi":"10.1007/s00213-024-06703-9","DOIUrl":"10.1007/s00213-024-06703-9","url":null,"abstract":"<p><strong>Rationale: </strong>The newly emerging synthetic cannabinoids (SCs) 5F-EDMB-PICA, CUMYL-PEGACLONE, and NM-2201 have been observed to produce effects by activating cannabinoid type 1 (CB1) receptors. Nevertheless, the pharmacological effects and potential for abuse of these three substances remain to be studied. These substances have yet to be regulated in many countries.</p><p><strong>Objectives: </strong>We investigated the safety, pharmacological effects, rewarding effects, and cannabinoid withdrawal of 5F-EDMB-PICA, CUMYL-PEGACLONE, and NM-2201.</p><p><strong>Methods: </strong>This study evaluated the drug safety and the cannabinoid-specific pharmacological effects of the three substances through acute toxicity experiments (in which the LD₅₀ of each substance was obtained) and tetrad experiments (comprising assessments of hypothermia, analgesia, locomotion inhibition, and catalepsy). Furthermore, the conditioned place preference (CPP) experiments and withdrawal experiments were conducted to evaluate the rewarding effect and cannabinoid withdrawal potential of the substances in question.</p><p><strong>Results: </strong>The results demonstrated that all three drugs exhibited certain acute toxic effects and could potentially induce tetrad effects. The data were analyzed using non-linear regression, and the corresponding ED₅₀ values and 95% confidence intervals (CI) were obtained. The rank order of potency was determined to be CUMYL-PEGACLONE > 5F-EDMB-PICA > NM-2201. In the CPP experiments, it was demonstrated that 5F-EDMB-PICA significantly induced an increase in CPP score at a dose of 0.3 mg/kg, while NM-2201 caused an increase in CPP score and a significant aversion effect at a dose of 2 and 3 mg/kg, respectively. It is noteworthy that all three types of SCs were observed to produce a significant biphasic effect, indicating that CPP scores were biphasic for all compounds. Following the administration of the CB1 receptor antagonist rimonabant, a notable increase in head twitches and paw tremors was observed, indicating that these three SCs induce cannabinoid withdrawal through the mediation of CB1 receptors.</p><p><strong>Conclusions: </strong>The results of this study indicated that these SCs possess cannabinoid-specific pharmacological effects and abuse potential, which provides substantial experimental data to support the future regulation of these substances.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"533-544"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473279","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":"Immediate effects of propofol on mood: a randomized comparison of two doses in a cohort with depression.","authors":"Daniel A Feldman, Keith G Jones, Lily C Vonesh, Rebecca Jacobs, Nathan Hoffman, Carter Lybbert, Jason Huang, Kai Kuck, David Odell, Scott C Tadler, Brian J Mickey","doi":"10.1007/s00213-024-06699-2","DOIUrl":"10.1007/s00213-024-06699-2","url":null,"abstract":"<p><strong>Rationale: </strong>The intravenous anesthetic propofol is known to induce positive mood effects during routine clinical use, suggesting it might be repurposed as an antidepressant, but also raising concerns about abuse potential. How propofol's acute effects vary by dose and with repeated infusions is unknown.</p><p><strong>Objectives: </strong>This exploratory analysis aimed to (1) compare the immediate mood effects of propofol administered at two different doses, (2) describe how those mood effects change with repeated infusions, and (3) evaluate whether acute mood improvement predicts later antidepressant response.</p><p><strong>Methods: </strong>Twenty-four adults with moderate-to-severe treatment-resistant depression were randomized into two dosing groups. Six low- or high-dose propofol infusions were administered under blinded conditions over a two-week period. Self-reported mood states were recorded before and after each infusion using the Positive and Negative Affect Schedule (PANAS-X). Abuse potential was evaluated with the Drug Effects Questionnaire (DEQ-5).</p><p><strong>Results: </strong>At the first infusion, propofol induced acute improvements in PANAS-X Sadness, Fear, Joviality, and Serenity scales (p < 0.002), independent of dose. Over the series of six infusions, acute changes in Sadness, Fear, and Joviality, but not Serenity, diminished with infusion number (p < 0.002). The DEQ-5 \"want more\" rating decreased across infusions (p = 0.002). Changes in PANAS-X scales with the first infusion did not predict later improvement in depression severity (p > 0.05).</p><p><strong>Conclusion: </strong>Cumulative changes in mood states observed with repeated infusions suggest that propofol engages adaptive mechanisms in mood circuitry. Subjective responses with repeated infusions do not indicate increasing potential for abuse in this patient population.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"481-495"},"PeriodicalIF":3.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473283","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}