Psychopharmacology最新文献

{"title":"Repeated exposure to novelty promotes resilience against the amyloid-beta effect through dopaminergic stimulation.","authors":"Cintia Velázquez-Delgado, Eduardo Hernández-Ortiz, Lucia Landa-Navarro, Miguel Tapia-Rodríguez, Perla Moreno-Castilla, Federico Bermúdez-Rattoni","doi":"10.1007/s00213-024-06650-5","DOIUrl":"10.1007/s00213-024-06650-5","url":null,"abstract":"<p><strong>Rationale: </strong>The accumulation of beta-amyloid peptide (Aβ) in the forebrain leads to cognitive dysfunction and neurodegeneration in Alzheimer's disease. Studies have shown that individuals with a consistently cognitively active lifestyle are less vulnerable to Aβ toxicity. Recent research has demonstrated that intrahippocampal Aβ can impact catecholaminergic release and spatial memory. Interestingly, exposure to novelty stimuli has been found to stimulate the release of catecholamines in the hippocampus. However, it remains uncertain whether repeated enhancing catecholamine activity can effectively alleviate cognitive impairment in individuals with Alzheimer's disease.</p><p><strong>Objectives: </strong>Our primary aim was to investigate whether repeated exposure to novelty could enable cognitive resilience against Aβ. This protection could be achieved by modulating catecholaminergic activity within the hippocampus.</p><p><strong>Methods: </strong>To investigate this hypothesis, we subjected mice to three different conditions-standard housing (SH), repeated novelty (Nov), or daily social interaction (Soc) for one month. We then infused saline solution (SS) or Aβ (Aβ_1-42) oligomers intrahippocampally and measured spatial memory retrieval in a Morris Water Maze (MWM). Stereological analysis and extracellular baseline dopamine levels using in vivo microdialysis were assessed in independent groups of mice.</p><p><strong>Results: </strong>The mice that received Aβ_1-42 intrahippocampal infusions and remained in SH or Soc conditions showed impaired spatial memory retrieval. In contrast, animals subjected to the Nov protocol demonstrated remarkable resilience, showing strong spatial memory expression even after Aβ_1-42 intrahippocampal infusion. The stereological analysis indicated that the Aβ_1-42 infusion reduced the tyrosine hydroxylase axonal length in SH or Soc mice compared to the Nov group. Accordingly, the hippocampal extracellular dopamine levels increased significantly in the Nov groups.</p><p><strong>Conclusions: </strong>These compelling results demonstrate the potential for repeated novelty exposure to strengthen the dopaminergic system and mitigate the toxic effects of Aβ_1-42. They also highlight new and promising therapeutic avenues for treating and preventing AD, especially in its early stages.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"85-100"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983116","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":"Escalation of intravenous fentanyl self-administration and assessment of withdrawal behavior in male and female mice.","authors":"Yueyi Chen, Tiange Xiao, Adam Kimbrough","doi":"10.1007/s00213-024-06739-x","DOIUrl":"https://doi.org/10.1007/s00213-024-06739-x","url":null,"abstract":"<p><strong>Rationale: </strong>The rise in overdose deaths from synthetic opioids, especially fentanyl, necessitates the development of preclinical models to study fentanyl use disorder (FUD). While there has been progress with rodent models, additional translationally relevant models are needed to examine excessive fentanyl intake and withdrawal signs.</p><p><strong>Objective: </strong>The current study aimed to develop a translationally relevant preclinical mouse model of FUD by employing chronic intravenous fentanyl self-administration (IVSA).</p><p><strong>Methods: </strong>The study performed intravenous self-administration (IVSA) of fentanyl in male and female C57BL/6J mice for 14 days. Mechanical pain sensitivity during withdrawal was assessed using the von Frey test. Anxiety-like behavior was evaluated via the open field test one week into abstinence, and drug seeking behavior after extended abstinence was assessed at four weeks abstinence.</p><p><strong>Results: </strong>Both male and female mice demonstrated a significant escalation in fentanyl intake over the 14 days of self-administration, with significant front-loading observed in the final days of self-administration. Mice showed increased mechanical pain sensitivity at 36 and 48hours withdrawal from fentanyl. At 1-week abstinence from fentanyl, mice exhibited increased anxiety-like behavior compared to naive mice. Four weeks into abstinence from fentanyl, mice maintained lever-pressing behavior on the previous reward-associated active lever, with significantly higher active lever pressing compared to inactive lever pressing.</p><p><strong>Conclusions: </strong>The study establishes a translationally relevant mouse model of IVSA of fentanyl, effectively encapsulating critical aspects of FUD, including escalation of drug intake, front-loading behavior, withdrawal signs, and drug-seeking behavior into extended abstinence. This model offers a robust basis for further exploration into behavioral and neurobiological mechanisms involved in fentanyl dependence and potential therapeutic strategies.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896996","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":"Discriminative stimulus properties of α-ethyltryptamine (α-ET) in rats: α-ET-like effects of MDMA, MDA and aryl-monomethoxy substituted derivatives of α-ET.","authors":"Carmen Abate, Richard Young, Malgorzata Dukat, Richard A Glennon","doi":"10.1007/s00213-024-06738-y","DOIUrl":"10.1007/s00213-024-06738-y","url":null,"abstract":"<p><p>Rationale α-ET (α-ethyltryptamine), a homolog of the classical hallucinogen α-methyltryptamine, was once prescribed clinically as an antidepressant. Classical psychedelic drugs are currently of interest as potential pharmacotherapy for psychiatric disorders. Objectives Drug discrimination was used to (a) determine if α-ET-like stimulus effects could be engendered by the prototypical phenylalkylamines MDMA (\"Ecstasy\") or MDA (\"Love Drug\") and (b) evaluate the α-ET-like stimulus effects of four synthesized aryl-substituted monomethoxy analogs of α-ET (4-OMe-, 5-OMe-, 6-OMe- and 7-OMe-α-ET). Methods Rats were trained to discriminate α-ET (2.5 mg/kg) from saline using a two-lever operant task. Results The α-ET (ED₅₀ = 1.04 mg/kg) stimulus generalized to MDMA (ED₅₀ = 0.72 mg/kg) and MDA (ED₅₀ = 0.48 mg/kg). The four α-ET derivatives produced various results; 4-OMe α-ET yielded negligible (20% maximum) α-ET-like responding; 5-OMe α-ET occasioned a modest level (40% maximum) of α-ET-like substitution; 6-OMe α-ET (ED₅₀ = 6.26 mg/kg) generalized completely, but in a narrow dose range and in an inverted U-shaped manner; 7-OMe α-ET (ED₅₀ = 2.78 mg/kg) generalized completely. Conclusions α-ET stimulus effects are similar to those of MDMA, but appear more closely aligned to those of MDA and are produced by its stereoisomers which, when combined, exert MDA/MDMA-, hallucinogen- and some stimulant-like stimulus actions. Thus, α-ET exerts a complex (compound) stimulus and appears to be a tryptamine counterpart of these prototypic phenylalkylamines. The monomethoxy analogs of α-ET produced an assortment of α-ET-like outcomes such that future investigations of these agents will likely need to be performed on an individual basis; extrapolations of α-ET-like effects to these analogs should be done judiciously.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896972","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":"Reduced sensitivity to cocaine effects and changes in mesocorticolimbic dopamine receptors in adolescent sexually active female rats.","authors":"Daniella Agrati, Gabriella Marin, Lucía Rehermann, Natalia Uriarte, Marta C Antonelli, Gabriela Bedó","doi":"10.1007/s00213-024-06741-3","DOIUrl":"https://doi.org/10.1007/s00213-024-06741-3","url":null,"abstract":"<p><strong>Rationale: </strong>The sexual behavior of the female rat is highly motivated, and the mesocorticolimbic dopaminergic system -involved in psychostimulants effects- has been implicated in its regulation. Female rats begin to express sexual behavior during adolescence, a period during which this system is not yet mature.</p><p><strong>Objective: </strong>To examine the impact of cocaine on sexual motivation and behavior of adolescent and adult female rats, and to determine the dopamine receptors binding in mesocorticolimbic areas of these females.</p><p><strong>Methods: </strong>The effect of acute administration of cocaine (0.0, 10.0, and 20.0 mg/kg, intraperitoneally) on the male´s incentive value for females and on their sexual behavior in late adolescent (45-55 days old) and adult (100-120 days old) rats was assessed during late proestrus. The binding of D1-like and D2-like receptors in the striatum and medial prefrontal cortex (mPFC) of adolescent and adult rats were determined by autoradiography.</p><p><strong>Results: </strong>Cocaine did not affect females´ preference for the male. However, 10 mg/kg of cocaine reduced the expression of sexual motivated responses and 20 mg/kg also diminished sexual receptivity exclusively in adult subjects. Moreover, cocaine-induced a more pronounced hyper-locomotion in adult than in late adolescent rats. Late adolescent females exhibited higher dopamine receptors binding in the mPFC and reduced D2-like receptors binding in the Nucleus Accumbens shell when compared to adults.</p><p><strong>Conclusions: </strong>Late adolescent females are less sensitive than adults to the detrimental effects of cocaine on sexual behavior and locomotion. This phenomenon is accompanied by variation in dopamine receptors in mesocorticolimbic areas affected by this psychostimulant.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142897012","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":"An exploratory study of the safety profile and neurocognitive function after single doses of mitragynine in humans.","authors":"Elisabeth Prevete, Eef L Theunissen, Kim P C Kuypers, Riccardo Paci, Johannes T Reckweg, Mauro Cavarra, Stefan W Toennes, Sabrina Ritscher, Giuseppe Bersani, Ornella Corazza, Massimo Pasquini, Johannes G Ramaekers","doi":"10.1007/s00213-024-06734-2","DOIUrl":"https://doi.org/10.1007/s00213-024-06734-2","url":null,"abstract":"<p><strong>Rationale: </strong>Despite the growing scientific interest on mitragynine, the primary alkaloid in kratom (Mitragyna Speciosa), there is a lack of clinical trials in humans.</p><p><strong>Objectives: </strong>This phase 1 study aimed to evaluate mitragynine's safety profile and acute effects on subjective drug experience, neurocognition, and pain tolerance.</p><p><strong>Methods: </strong>A placebo-controlled, single-blind, within-subjects study was conducted in two parts. In part A, eight healthy human volunteers received placebo and three doses of mitragynine (5, 10, and 20 mg) in a sequential dosing scheme, on separate days. In part B, a second group of seven volunteers received placebo and 40 mg of mitragynine. Vital signs, subjective drug experience, neurocognitive function, and pain tolerance were measured at regular intervals for 7 h after administration.</p><p><strong>Results: </strong>Overall, mitragynine did not affect most of the outcome measures at any dose. Yet, the lowest dose (5 mg) of mitragynine increased subjective ratings of arousal and attention, accuracy in a sustained attention task, and motor inhibition. The highest dose (40 mg) of mitragynine increased subjective ratings of amnesia and produced mild psychopathological symptoms. Mitragynine did not significantly affect vital signs, and only mild, transient side effects were reported.</p><p><strong>Conclusion: </strong>The present study suggests that low doses (5-10 mg) of mitragynine may cause subjective feelings of stimulation and enhance attention, while the highest dose (40 mg) may cause inhibitory feelings of amnesia and distress. Mitragynine doses up to 40 mg were well tolerated in this group.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142897035","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":"Ethanol self-administration targets GluA2-containing AMPA receptor expression and synaptic activity in the nucleus accumbens in a manner that drives the positive reinforcing properties of the drug.","authors":"Sara Faccidomo, Briana L Saunders, Ashley M May, Vallari R Eastman, Michelle Kim, Seth M Taylor, Jessica L Hoffman, Zoé A McElligott, Clyde W Hodge","doi":"10.1007/s00213-024-06740-4","DOIUrl":"https://doi.org/10.1007/s00213-024-06740-4","url":null,"abstract":"<p><strong>Rationale: </strong>The positive reinforcing effects of alcohol (ethanol) drive repetitive use and contribute to alcohol use disorder (AUD). Ethanol alters the expression of glutamate AMPA receptor (AMPAR) subunits in reward-related brain regions, but the extent to which this effect regulates ethanol's reinforcing properties is unclear.</p><p><strong>Objective: </strong>This study investigates whether ethanol self-administration changes AMPAR subunit expression and synaptic activity in the nucleus accumbens core (AcbC) to regulate ethanol's reinforcing effects in male C57BL/6 J mice.</p><p><strong>Results: </strong>Sucrose-sweetened ethanol self-administration (0.81 g/kg/day) increased AMPAR GluA2 protein expression in the AcbC, without effect on GluA1, compared to sucrose-only controls. Infusion of myristoylated Pep2m in the AcbC, which blocks GluA2 binding to N-ethylmaleimide-sensitive fusion protein (NSF) and reduces GluA2-containing AMPAR activity, reduced ethanol-reinforced responding without affecting sucrose-only self-administration or motor activity. Antagonizing GluA2-lacking AMPARs, through AcbC infusion of NASPM, had no effect on ethanol self-administration. AcbC neurons receiving projections from the basolateral amygdala (BLA) showed increased sEPSC area under the curve (a measurement of charge transfer) and slower decay kinetics in ethanol self-administering mice as compared to sucrose. Optogenetic activation of these neurons revealed an ethanol-enhanced AMPA/NMDA ratio and significantly reduced paired-pulse ratio, suggesting elevated GluA2 contributions specifically within the BLA➔AcbC pathway.</p><p><strong>Conclusions: </strong>Ethanol use upregulates GluA2 protein expression in the AcbC and AMPAR synaptic activity in AcbC neurons receiving BLA projections and enhances synaptic plasticity directly within the BLA➔AcbC circuit. GluA2-containing AMPAR activity in the AcbC regulates the positive reinforcing effects of ethanol through an NSF-dependent mechanism, highlighting a potential therapeutic target in AUD.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877751","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":"Working memory processes and the histamine-3 receptor in schizophrenia: a [¹¹C]MK-8278 PET-fMRI study.","authors":"Atheeshaan Arumuham, Ekaterina Shatalina, Matthew M Nour, Mattia Veronese, Ellis Chika Onwordi, Stephen J Kaar, Sameer Jauhar, Eugenii A Rabiner, Oliver D Howes","doi":"10.1007/s00213-024-06730-6","DOIUrl":"https://doi.org/10.1007/s00213-024-06730-6","url":null,"abstract":"<p><strong>Rationale: </strong>Working memory impairment is a prominent feature of schizophrenia which predicts clinical and functional outcomes. Preclinical data suggest histamine-3 receptor (H3R) expression in cortical pyramidal neurons may have a role in working memory, and post-mortem data has found disruptions of H3R expression in schizophrenia.</p><p><strong>Objectives: </strong>We examined the role of H3R in vivo to elucidate its role on working memory impairment in schizophrenia.</p><p><strong>Methods: </strong>We used positron emission tomography (PET) with the selective H3R radioligand [¹¹C]MK-8278 to measure H3R availability, and employed a task during functional magnetic resonance imaging (fMRI) to assess working memory-evoked brain activation and cognitive task performance, in patients with schizophrenia (n = 12) and matched healthy volunteers (n = 12). We assessed the relationship between H3R availability and both task performance and working memory-evoked brain activation in regions of interest (ROIs), including the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC).</p><p><strong>Results: </strong>Patients with schizophrenia showed a strong positive correlation, after corrections for multiple comparisons, between ACC H3R availability and task performance (rho = 0.73, p = 0.007), which was absent in the control group (rho = 0.03, p = 0.94). Further ROI analysis did not find a significant relationship between H3R availability and working memory-evoked brain activation.</p><p><strong>Conclusions: </strong>These results provide support for the role of H3R on working memory processes in patients with schizophrenia.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877753","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":"Glutathione alterations in depression: a meta-analysis and systematic review of proton magnetic resonance spectroscopy studies.","authors":"Charles J M Bell, Mitul Mehta, Luwaiza Mirza, Allan H Young, Katherine Beck","doi":"10.1007/s00213-024-06735-1","DOIUrl":"https://doi.org/10.1007/s00213-024-06735-1","url":null,"abstract":"<p><strong>Background: </strong>Major depressive disorder (MDD) is a common and serious psychiatric disorder associated with significant morbidity. There is mounting evidence for the role of oxidative stress in the pathophysiology of depression.</p><p><strong>Objective: </strong>To investigate alterations in the brain antioxidant glutathione in depression by undertaking a meta-analysis of proton magnetic resonance spectroscopy (1H-MRS).</p><p><strong>Methods: </strong>MEDLINE, EMBASE and Psych Info databases were searched for case-control studies that reported brain glutathione levels in patients with depression and healthy controls. Means and variances (SDS) were extracted for each measure to calculate effect sizes. Hedges g was used to quantify mean differences. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed.</p><p><strong>Results: </strong>8 studies that reported measurements for 230 patients with depression and 216 controls were included. Three studies included data for the occipital cortex and five studies for the medial frontal cortex. In the occipital cortex, GSH was lower in the patient group as compared to controls (g = -0.98, 95% [CI, -1.45--0.50], P = < 0.001). In both the medial frontal cortex and in the combined all areas analysis there was no significant difference in GSH levels between cases and controls.</p><p><strong>Conclusions: </strong>This study found reduced levels of GSH specifically in the occipital region of patients with MDD. This provides some support for the role of oxidative stress in depression and suggests that targeting this system may provide future therapeutic opportunities. However, the meta-analysis was limited by the small number and quality of the included studies. More studies using high quality MRS methods in a variety of brain regions are needed in the future to test this putative hypothesis.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872802","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":"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":"https://doi.org/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":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-20","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":"Repeated toluene inhalation in male and female adolescent rats induces persistent drug preference and impairs cognitive and social behavior.","authors":"Joannes Luke B Asis, Ajina C Carampel, Jariel Naomi B Bacar, Johanna C Munar, Cynthia Grace C Gregorio, Paul Mark B Medina, Leslie Michelle M Dalmacio, Jesus Emmanuel A D Sevilleja, Gregory J Quirk, Rohani Cena-Navarro","doi":"10.1007/s00213-024-06731-5","DOIUrl":"https://doi.org/10.1007/s00213-024-06731-5","url":null,"abstract":"<p><strong>Rationale: </strong>Adolescent inhalant use is an understudied and undertreated disorder, particularly in females. Chronic exposure to inhalants, like toluene, can have long-lasting effects on behavior. However, most animal studies lack the incorporation of both sexes and do not focus on the abstinence period.</p><p><strong>Objective: </strong>We assessed the behavioral effects during prolonged abstinence following repeated toluene inhalation in adolescent male and female rats.</p><p><strong>Methods: </strong>We repeatedly exposed adolescent male and female Sprague Dawley rats to toluene vapor (1500 or 3000 ppm) for 6 days using the conditioned place preference (CPP) procedure. We tested drug-associated context preference, locomotion, anxiety-like behavior, object memory, social preference, and cognitive flexibility across 22 days of abstinence.</p><p><strong>Results: </strong>In females, 3000 ppm toluene increased CPP on days 8 and 22 of abstinence but this effect did not reach significance in males. Instead, males showed a significant increase in locomotion on days 7 and 21. Toluene also impaired social novelty preference and reversal learning during long-term abstinence, but not anxiety-like behavior or object recognition memory.</p><p><strong>Conclusions: </strong>Our rodent findings suggest that female inhalant users may show persistent drug preference during abstinence following chronic use. Furthermore, prolonged cognitive and social deficits should be addressed in treatment programs for adolescents.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847552","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}