Journal of Psychopharmacology最新文献

{"title":"Effects of acute alcohol consumption on hostile attribution bias towards emotional facial expressions and implicit approach/avoidance tendencies.","authors":"Andrew P R Eastwood, Ian S Penton-Voak, Marcus R Munafò, Angela S Attwood","doi":"10.1177/02698811251408743","DOIUrl":"10.1177/02698811251408743","url":null,"abstract":"<p><strong>Background: </strong>Research suggests that a greater perception of hostility in social cues increases aggression, and alcohol influences perception of social cues. Taken together, this could explain some instances of alcohol-related aggression. This study investigated whether social drinkers interpret faces as more hostile following acute alcohol compared to placebo, and whether alcohol influences the tendency to approach or avoid emotional facial expressions.</p><p><strong>Methods: </strong>Regular non-dependent drinkers (<i>N</i> = 84) participated in a double-blind placebo-controlled experiment. Participants completed two sessions and were tested following an alcoholic drink (0.4 g/kg), and matched placebo. In each session, they completed tasks measuring hostile attribution bias (HAB) towards emotional faces (happy, sad, angry, disgust, surprise, and fear), and approach/avoidance tendencies towards emotional faces (angry, happy, sad and disgust).</p><p><strong>Results: </strong>Alcohol did not affect global hostility ratings of emotional facial expression (<i>p</i> = 0.342). However, it did increase global hostility ratings of ambiguous emotional faces after alcohol (drink by intensity interaction; <i>p</i> = 0.002). At an emotion-specific level, happy faces were seen as more hostile after alcohol when compared to placebo (<i>p</i> = 0.009; irrespective of emotional intensity). Alcohol did not affect approach/avoidance tendencies when seeing emotional faces following alcohol.</p><p><strong>Conclusions: </strong>These findings suggest that alcohol increases hostile judgements of ambiguous emotional faces. They also suggest that happy faces are perceived to be more hostile following alcohol. As an increased HAB when processing socially relevant information increases aggressive responding, this increased hostile perception of happy faces following alcohol may increase the likelihood of aggressive behaviour.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1392-1404"},"PeriodicalIF":5.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499246","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 effects of transcranial direct current stimulation (tDCS) on subjective, autonomic and neuropsychological response in the 7.5% CO₂ experimental model of anxiety.","authors":"Joanna Astrid Miler, Daniel Meron, David S Baldwin, Matthew Garner","doi":"10.1177/02698811261420089","DOIUrl":"10.1177/02698811261420089","url":null,"abstract":"<p><strong>Background: </strong>Anxiety is characterized by hypervigilance, distractibility and selective processing of negative information. There is growing evidence that prefrontal function underlies biases in threat processing and attention control in anxiety. We examined the effect of 20 min of 2 mA dorsolateral prefrontal cortex transcranial direct current stimulation (tDCS) (bipolar-balanced montage) on subjective anxiety, autonomic arousal and threat processing in the 7.5% CO₂ experimental medicine model of anxiety.</p><p><strong>Methods: </strong>A between-subjects healthy volunteer double-blind randomized design compared 2 mA tDCS stimulation of the PFC versus sham tDCS on subjective anxiety, autonomic arousal and antisaccade performance during 7.5% CO₂ challenge.</p><p><strong>Results: </strong>tDCS did not moderate subjective and autonomic response to CO₂ challenge. tDCS reduced erroneous eye movements toward threat images relative to neutral images.</p><p><strong>Conclusion: </strong>Twenty minutes of active 2 mA tDCS over the left dorsolateral prefrontal cortex may reduce threat processing biases during experimentally induced anxiety and could help target early positive changes in emotion processing.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1446-1455"},"PeriodicalIF":5.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433809","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":"Central nervous system acting medication used by young adults with borderline personality disorder in Sweden 2006-2019.","authors":"Annika Tiger, Yasmina Molero, Isabell Brikell, Zheng Chang, Paul Lichtenstein, Henrik Larsson, Brian M D'Onofrio, Clara Hellner, Tyra Lagerberg, Nitya Jayaram-Lindström, Ralf Kuja-Halkola","doi":"10.1177/02698811251413479","DOIUrl":"10.1177/02698811251413479","url":null,"abstract":"<p><strong>Background: </strong>Most individuals diagnosed with borderline personality disorder (BPD) use psychotropic medications. BPD symptom severity is elevated in young adulthood, but medication utilisation studies in young adults with BPD are lacking.</p><p><strong>Aims: </strong>To investigate the use of central nervous system (CNS) acting medications among young adults (aged 18-24), who were diagnosed with BPD, focusing on the years around the first established diagnosis.</p><p><strong>Methods: </strong>A cohort study of all individuals with a registered BPD diagnosis in Sweden was conducted using national population register data. Dispensed prescriptions between July 2005 and June 2020 were utilised. Prevalent use, long-term use, and co-medication were investigated during specific 1-year periods: the year before, and then the first, second, and third year after diagnosis.</p><p><strong>Results: </strong>Medication use peaked for all three measures in the year following the first BPD diagnosis: 90.3% used CNS-acting medication during that year, and antidepressants were the most used group (70.1%). Furthermore, 74.5% used medication for >12 months, and 34.8% used ⩾3 medication groups in co-medication. Compared to a reference group of individuals diagnosed with depression, the BPD group used more medication. In the depression group, 87.5% used medication, 55.2% used medication for >12 months, and 3.8% used ⩾3 medication groups in co-medication. Moreover, medication use increased from 2006 to 2019.</p><p><strong>Conclusion: </strong>This indicates the importance of continuously evaluating risks and benefits with medication use, and in having easy access to up-to-date guidance about best clinical practice for individuals diagnosed with BPD, to facilitate appropriate and safe medication use.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1343-1351"},"PeriodicalIF":5.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202011","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":"Negative affect interacts with perceptual affective biases.","authors":"Thomas Murray, Rebecca P Lawson","doi":"10.1177/02698811251409143","DOIUrl":"10.1177/02698811251409143","url":null,"abstract":"<p><strong>Background: </strong>Affective biases are central to mood and anxiety disorders, with individuals often interpreting ambiguous facial expressions more negatively. Adaptation paradigms, where exposure to emotional stimuli shifts perception, provide a tool to separate perceptual from decisional biases, but have not been used to study emotional biases relevant to affective disorders.</p><p><strong>Aims: </strong>To determine whether affective biases in facial emotion perception arise from perceptual or decisional processes, and to examine how these biases are modulated by individual differences in negative affect.</p><p><strong>Methods: </strong>Eighty participants completed emotion and identity discrimination tasks before and after adaptation. Participants made binary judgements of morphed facial expressions (happy/sad) and identities (Bonny/Sheila), followed by confidence ratings. Logistic and Gaussian functions were used to estimate adaptation effects from shifts in the point of subjective equality (PSE) and peak uncertainty.</p><p><strong>Results/outcomes: </strong>Adaptation produced repulsive aftereffects: exposure to happy faces biased perception towards sadness, and vice versa, with analogous effects for identity. Correlated shifts in PSE and uncertainty indicated a perceptual rather than decisional origin. Negative affect (derived from Beck Depression Inventory and State Trait Anxiety Inventory-trait questionnaires) moderated this relationship, such that individuals higher in negative affect showed stronger perceptual biases towards sadness.</p><p><strong>Conclusions/interpretation: </strong>Findings suggest that negative affect modulates low-level perceptual encoding of emotional expressions. This supports cognitive neuropsychological models positing that antidepressants first target early perceptual biases and highlight perceptual encoding as a potential mechanism underlying affective biases in mood and anxiety disorders.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1405-1414"},"PeriodicalIF":5.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100023","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":"Association of polygenic risk for cannabis use disorder with brain structure among youth with and without bipolar disorder.","authors":"Alysha A Sultan, Clement C Zai, Kody G Kennedy, L Trevor Young, Bradley J MacIntosh, Benjamin I Goldstein","doi":"10.1177/02698811261424206","DOIUrl":"10.1177/02698811261424206","url":null,"abstract":"<p><strong>Background: </strong>Cannabis use disorder (CUD) is common in youth, with elevated rates among youth with bipolar disorder (BD). Cannabis use among youth is also associated with anomalous neurostructural phenotypes. While neurophysiological mechanisms associated with cannabis use may contribute to these differences, genetic predisposition to CUD may also be contributory. Given the lack of prior studies on this topic, we examined polygenic risk scores for CUD (CUD-PRS) in relation to brain structure among youth with and without BD.</p><p><strong>Methods: </strong><i>T</i>₁-weighted magnetic resonance imaging (MRI) was collected for 114 participants ages 13-20 (<i>n</i> = 67 BD, <i>n</i> = 47 healthy controls (HC)). CUD-PRS was calculated using PRS-CS-auto, based on summary statistics from a genome-wide association study conducted in adults. Covariate-adjusted vertex-wise analyses examined the association of CUD-PRS with cortical volume, surface area (SA), and thickness in the whole sample, and within BD and HC.</p><p><strong>Results: </strong>In the whole sample, higher CUD-PRS was associated with significantly lower volume and SA in the right superior frontal gyrus (β = -0.31, <i>p</i> < 0.01; β = -0.33, <i>p</i> < 0.01), and with significantly lower SA in the left paracentral lobule (β = -0.37, <i>p</i> = 0.0002). Within HC, higher CUD-PRS was associated with significantly lower volume and SA in the left and right superior frontal gyrus (β = -0.78, <i>p</i> < 0.002; β = -0.66, <i>p</i> < 0.028; β = -0.79, <i>p</i> < 0.0001; β = -0.68, <i>p</i> < 0.0001). There were no significant within-BD results.</p><p><strong>Conclusion: </strong>Present findings demonstrate a consistent pattern of higher CUD-PRS corresponding with lower regional brain structure, even in the absence of CUD. Future studies are needed to understand the mechanisms, developmental trajectories, and diagnosis-related differences in the observed findings.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1456-1466"},"PeriodicalIF":5.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147307091","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":"Reinstatement of escitalopram and clonidine administration reverses the cessation-induced enhanced activation of rat norepinephrine and serotonin neuronal firing activity.","authors":"Mostafa El Mansari, Naomichi Okamoto, Pierre Blier","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Abrupt cessation of serotonin (5-HT) reuptake inhibitors (SRIs) in men and women induces a constellation of somatic and psychological symptoms known as discontinuation SRI syndrome; however, the underlying neurophysiological mechanisms remain unclear.</p><p><strong>Aims: </strong>While previous work has largely focused on 5-HT dysregulation, this study assessed whether norepinephrine (NE) signalling may play a critical role.</p><p><strong>Methods: </strong>Using in vivo electrophysiology, the firing activity of locus coeruleus NE and dorsal raphe nucleus 5-HT neurons was examined in male rats following sustained escitalopram administration for 14 days and its subsequent cessation for 2 days to allow its elimination.</p><p><strong>Results: </strong>Escitalopram cessation produced a marked increase in the suppressed firing rate of NE neurons and a doubling of the normalized firing rate of 5-HT neurons. Acute intravenous injection of escitalopram restored the firing rate of both neuronal populations to their prior firing levels after the drug had been administered for 14 days. Acute intravenous injection of the α₂-adrenoceptor agonist clonidine had the same effect as the re-introduction of escitalopram on both populations of neurons.</p><p><strong>Conclusions: </strong>These results show that abrupt cessation of the SRI escitalopram resulted in robust overactivation of both NE and 5-HT neurons. Normalization of the SRI cessation-induced overactivation of NE and 5-HT neurons by the acute inhibition of the 5-HT reuptake transporter is consistent with the rapid relief of discontinuation symptoms observed in patients resuming their SRI. A similar effect of clonidine on NE and 5-HT neuronal firing would support its use in managing discontinuation symptoms seen after SRI cessation.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811261478602"},"PeriodicalIF":5.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865612","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 empathogen 3,4-methylenedioxymethamphetamine, but not methamphetamine, increases feelings of global trust.","authors":"Ramona L Martinez, Nina Radošić, Hanna Molla, Harriet de Wit, Sonja Lyubomirsky","doi":"10.1177/02698811251370999","DOIUrl":"10.1177/02698811251370999","url":null,"abstract":"<p><strong>Background: </strong>The empathogen and psychostimulant 3,4-methylenedioxymethamphetamine (MDMA) is thought to boost both subjective well-being and social connection. Although MDMA is considered to enhance social connection to a greater extent than other stimulant drugs, few studies have compared MDMA to other stimulants. In addition, previous studies have focused on social positivity effects (e.g., increased trust) for specific in-lab interaction partners without considering more generalized social positivity effects (e.g., trust in one's community).</p><p><strong>Aims: </strong>We tested the effects of MDMA on subjective ratings of well-being and global social connection, including feelings of trust toward one's community and society. The effects of MDMA were compared to a prototypic stimulant, methamphetamine (MA).</p><p><strong>Methods: </strong>Across two studies, we examined differences in subjective well-being and global social well-being 90 minutes after a conversation on MDMA (study 1; <i>N</i> = 15; 100 mg) and after a conversation on MA (study 2; <i>N</i> = 20; 20 mg) compared to a placebo.</p><p><strong>Results: </strong>After MDMA, participants reported significantly higher global trust, <i>t</i>(14) = -2.583, <i>p</i> = 0.022, and marginally higher self-worth, <i>t</i>(14) = -2.000, <i>p</i> = 0.065, compared with after the placebo. Furthermore, MA did not alter scores of subjective well-being and social connection.</p><p><strong>Conclusions: </strong>Our findings extend previous research by demonstrating that MDMA increases feelings of trust in the social world beyond lab-specific interaction partners. These findings are consistent with user reports of generalized social well-being effects and support the idea that MDMA may have clinical value from a social psychological perspective.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1361-1367"},"PeriodicalIF":5.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075553","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 impact of antidepressant use on MDMA fatalities: A matched case-control study using a post-mortem database.","authors":"Kirsten L Rock, Paul Rees, David Morgan, Caroline S Copeland","doi":"10.1177/02698811261436573","DOIUrl":"10.1177/02698811261436573","url":null,"abstract":"<p><strong>Background: </strong>3,4-methylenedioxymethamphetamine (MDMA) is being investigated as a new therapy for post-traumatic stress disorder (PTSD). With antidepressants as the first-line pharmacotherapy for PTSD, it is important to understand any drug-drug interactions between antidepressants and MDMA. This study aimed to investigate the association between antidepressant use and MDMA fatality using a drug-death database.</p><p><strong>Methods: </strong>A retrospective case-control study was performed using a dataset from the National Programme on Substance Use Mortality. Deaths reported between 1997 and May 2023 were extracted. Cases were defined as deaths with MDMA detected and were age- and sex-matched to controls, defined as deaths with no MDMA detected. Cases were analysed by post-mortem (PM) detection of antidepressants and prescription of antidepressants. Conditional logistic regression was performed, adjusted for confounders (polysubstance use and intentionality of death).</p><p><strong>Results: </strong>A total of 1328 cases and 5312 matched controls for the PM analysis and 840 cases and 3360 matched controls for the prescribed analysis were included. In the PM analysis, after adjusting for potential confounders, antidepressant use was less likely in MDMA fatalities compared to other drug-related deaths (adjusted OR [aOR] 0.595 [95% Confidence interval (CI) 0.491-0.722]). In the prescribed analysis, there was no significant association between the prescription of antidepressants and MDMA fatalities (aOR 0.838 [95% CI 0.688-1.021]).</p><p><strong>Conclusions: </strong>An inverse association was found between antidepressant use and MDMA fatality in this retrospective case-control study using a drug-death database.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1352-1360"},"PeriodicalIF":5.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627092","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":"Pharmacological characterization of 4-F-3-Me-α-PVP: A novel synthetic cathinone with psychostimulant effects and abuse liability in rodents.","authors":"Núria Nadal-Gratacós, Stephanie Pain, Sandra Mata, Pol Puigseslloses, Morgane De Macedo, Virginie Lardeux, Fu-Hua Wang, Liselott Källsten, David Pubill, Xavier Berzosa, Jan Kehr, Marcello Solinas, Elena Escubedo, Jordi Camarasa, Raul López-Arnau","doi":"10.1177/02698811261430492","DOIUrl":"10.1177/02698811261430492","url":null,"abstract":"<p><strong>Background: </strong>The continual emergence of novel synthetic cathinones poses significant public health concerns due to their unpredictable pharmacological profiles and potential for abuse. Among these, 4-F-3-Me-α-PVP-a newly identified analogue of α-PVP-has recently surfaced on the illicit drug market, yet its biological effects remain uncharacterized.</p><p><strong>Aim: </strong>To provide the first comprehensive pharmacological evaluation of 4-F-3-Me-α-PVP.</p><p><strong>Methods: </strong>In vitro transporter inhibition was assessed using HEK293 cells expressing human dopamine (DA), norepinephrine, and serotonin transporter (DAT, NET, or SERT). In male rodents, locomotor activity was measured after i.p. (mice) or s.c. (rats) administration. In vivo microdialysis in rats quantified extracellular DA in the nucleus accumbens. Rewarding and reinforcing effects were evaluated using conditioned place preference (CPP) in mice and intravenous self-administration (IVSA) in rats under fixed-ratio and progressive-ratio schedules.</p><p><strong>Results: </strong>In vitro assays revealed that 4-F-3-Me-α-PVP acts as a potent DAT and NET inhibitor, with additional, though weaker, activity at SERT. In vivo, 4-F-3-Me-α-PVP significantly increased locomotor activity in male rodents (10 and 30 mg/kg in mice; 3 mg/kg in rats). Importantly, 4-F-3-Me-α-PVP also increased extracellular DA levels in the rat nucleus accumbens (3 mg/kg, s.c.), pointing to its potential for abuse. Behavioral assays further demonstrated rewarding and reinforcing effects in rodents, with significant CPP in mice at all doses tested and dose-dependent IVSA in rats observed under both fixed-ratio and progressive-ratio schedules.</p><p><strong>Conclusions: </strong>Collectively, these findings indicate that 4-F-3-Me-α-PVP possesses substantial psychostimulant and abuse-related effects in rodents, underscoring the need for regulatory vigilance and continued investigation into emerging synthetic cathinones.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1506-1518"},"PeriodicalIF":5.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147458005","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":"Administration of an extrasynaptic δ-subunit GABA_A receptor agonist in the prelimbic cortex attenuates methamphetamine sensitisation and relapse to methamphetamine-seeking behaviour in male rats.","authors":"Maarten van den Buuse, Jessica Roberts, Michael T C Hunter, Gracie L Hay, Nicholas A Everett, Sarah J Baracz, Travis A Wearne, Jennifer L Cornish","doi":"10.1177/02698811261430509","DOIUrl":"10.1177/02698811261430509","url":null,"abstract":"<p><strong>Aims: </strong>Chronic methamphetamine (METH) intake is associated with a high risk of psychosis and high susceptibility to relapse following abstinence. Prelimbic cortex (PLC) extrasynaptic GABA_A receptors containing the δ-subunit may be involved in the long-term effects of METH. We therefore investigated the effects of intra-PLC injection of the δ-subunit GABA_A receptor agonist 4,5,6,7-tetrahydroisoxazolo (5,4-c)pyridine-3(-ol) (THIP), on METH sensitisation, a model of METH psychosis, or relapse to METH seeking behaviour following extinction of intravenous self-administration.</p><p><strong>Methods and results: </strong>In Experiment 1, male rats received 1 week of chronic treatment with METH (1 mg/kg days 1 and 7, 5 mg/kg days 2-6) or saline, followed by 14 days withdrawal. THIP (0, 0.1, 0.3 or 1.0 μg per hemisphere) was then micro-injected into the PLC prior to challenge with METH (1 mg/kg) or saline. Acute METH challenge enhanced locomotor hyperactivity in METH-pretreated rats, confirming sensitisation. THIP administration into the PLC dose-dependently reduced the effect of acute METH challenge in METH-pretreated rats. In Experiment 2, rats were trained to intravenously self-administer METH, followed by 2 weeks of extinction. Rats were then given a METH priming injection or exposed to cues associated with METH self-administration, both of which reinstated responding on the lever previously paired with METH delivery. At the 0.3 µg dose, injection of THIP into the PLC reduced reinstatement responding in both paradigms.</p><p><strong>Conclusion: </strong>Selective activation of extrasynaptic PLC δ-subunit GABA_A receptors reduced METH sensitisation and drug primed or cue-induced METH-seeking behaviour. These findings may aid development of effective pharmacotherapies for treating chronic METH use.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"1480-1492"},"PeriodicalIF":5.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574386","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}