Addiction Biology最新文献

{"title":"Mapping structural covariance networks of emotional withdrawal symptoms in males with methamphetamine use disorder during abstinence","authors":"Xian Mo,&nbsp;Ping Jiang,&nbsp;Jiayu Sun,&nbsp;Lu Lu,&nbsp;Lei Li,&nbsp;Xiaoqi Huang,&nbsp;Jiajun Xu,&nbsp;Jing Li,&nbsp;Junran Zhang,&nbsp;Qiyong Gong","doi":"10.1111/adb.13394","DOIUrl":"https://doi.org/10.1111/adb.13394","url":null,"abstract":"<p>Individuals with methamphetamine use disorder (MUD) often experience anxiety and depressive symptoms during abstinence, which can worsen the likelihood of relapse. Thus, it is essential to understand the neuro-mechanism behind methamphetamine use and its associated emotional withdrawal symptoms in order to develop effective clinical strategies. This study aimed to evaluate associations between emotional withdrawal symptoms and structural covariance networks (SCNs) based on cortical thickness (CTh) across the brain. The CTh measures were obtained from Tl-weighted MRI data from a sample of 48 males with MUD during abstinence and 48 male healthy controls. The severity of anxiety and depressive symptoms was assessed by the Hamilton Anxiety Scale (HAMA) and depression (HAMD) scales. Two important nodes belonging to the brain reward system, the right rostral anterior cingulate cortex (rACC) and medial prefrontal cortex (medPFC), were selected as seeds to conduct SCNs and modulation analysis by emotional symptoms. MUDs showed higher structural covariance between the right rACC and regions in the dorsal attention, right frontoparietal, auditory, visual and limbic networks. They also displayed higher structural covariance between the right medPFC and regions in the limbic network. Moreover, the modulation analysis showed that higher scores on HAMA were associated with increased covariance between the right rACC and the left parahippocampal and isthmus cingulate cortex in the default mode network. These outcomes shed light on the complex neurobiological mechanisms underlying methamphetamine use and its associated emotional withdrawal symptoms and may provide new insights into the development of effective treatments for MUD.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13394","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140559526","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":"Substance use patterns, quantities, and associated risk factors in women with polysubstance misuse","authors":"Nia Fogelman,&nbsp;Marshall Tate,&nbsp;Stephanie Wemm,&nbsp;Liam Sullivan,&nbsp;Rachel Hart,&nbsp;Erin Vacey,&nbsp;Helen C. Fox,&nbsp;Rajita Sinha","doi":"10.1111/adb.13390","DOIUrl":"https://doi.org/10.1111/adb.13390","url":null,"abstract":"<p>Polysubstance use (PSU), the use of two or more substances proximally, is highly prevalent and has amplified the risk for morbidity and mortality. However, PSU patterns and associated risk factors are not well characterized. This may be especially relevant to women who are known to be vulnerable to stress/trauma, craving, pain, and anxious and depressive symptoms as associated risk factors for PSU. A cross-sectional observational study was conducted to characterize substance use patterns in women who regularly used cocaine, opioids, marijuana, alcohol, benzodiazepines and/or nicotine and were being assessed for a placebo-controlled study of guanfacine treatment (<i>n</i> = 94; ages 19–65). Data on stress/traumatic life events, drug cravings for each substance, pain ratings, and anxiety and depressive symptoms were also obtained using standardized well-validated surveys. High use per day of two or more drugs was observed (72.7% ± 33.3%) and opioid amounts were high relative to other drug amounts (<i>p</i>'s &lt; 0.001). Notably, higher stress/trauma events and higher cravings are each associated with cumulative PSU days, amounts and probability of an individual PSU day (<i>p</i>'s &lt; 0.02). This remained when PSU versus single substance use was compared. Pain, anxiety and depressive symptoms were not associated with PSU metrics. These findings characterize specific patterns of PSU in women and show that average drug craving and stress/trauma events are associated with PSU. Interventions that focus on stress/trauma and craving management could be of benefit in reducing PSU risk in women.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13390","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140552982","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 potential of 5-methoxy-N,N-dimethyltryptamine in the treatment of alcohol use disorder: A first look at therapeutic mechanisms of action","authors":"Stephan C. Tap","doi":"10.1111/adb.13386","DOIUrl":"https://doi.org/10.1111/adb.13386","url":null,"abstract":"<p>Alcohol use disorder (AUD) remains one of the most prevalent psychiatric disorders worldwide with high economic costs. Current treatment options show modest efficacy and relapse rates are high. Furthermore, there are increases in the treatment gap and few new medications have been approved in the past 20 years. Recently, psychedelic-assisted therapy with psilocybin and lysergic acid diethylamide has garnered significant attention in the treatment of AUD. Yet, they require significant amounts of therapist input due to prolonged subjective effects (~4–12 h) leading to high costs and impeding implementation. Accordingly, there is an increasing interest in the rapid and short-acting psychedelic 5-methoxy-<i>N,N</i>-dimethyltryptamine (5-MeO-DMT). This paper offers a first look at potential therapeutic mechanisms for AUD by reviewing the current literature on 5-MeO-DMT. Primarily, 5-MeO-DMT is able to induce mystical experiences and ego-dissolution together with increases in psychological flexibility and mindfulness. This could decrease AUD symptoms through the alleviation of psychiatric mood-related comorbidities consistent with the negative reinforcement and self-medication paradigms. In addition, preliminary evidence indicates that 5-MeO-DMT modulates neural oscillations that might subserve ego-dissolution (increases in <i>gamma</i>), psychological flexibility and mindfulness (increases in <i>theta</i>), and the reorganization of executive control networks (increases in coherence across frequencies) that could improve emotion regulation and inhibition. Finally, animal studies show that 5-MeO-DMT is characterized by neuroplasticity, anti-inflammation, 5-HT_2A receptor agonism, and downregulation of metabotropic glutamate receptor 5 with clinical implications for AUD and psychiatric mood-related comorbidities. The paper concludes with several recommendations for future research to establish the purported therapeutic mechanisms of action.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13386","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140544441","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":"Does compulsion explain addiction?","authors":"Andreas Heinz,&nbsp;Stefan Gutwinski,&nbsp;Nadja Samia Bahr,&nbsp;Rainer Spanagel,&nbsp;Gaetano Di Chiara","doi":"10.1111/adb.13379","DOIUrl":"https://doi.org/10.1111/adb.13379","url":null,"abstract":"<p>One of the leading drug addiction theories states that habits and the underlying neural process of a ventral to dorsal striatal shift are the building blocks of compulsive drug-seeking behaviour and that compulsion is the maladaptive persistence of responding despite adverse consequences. Here we discuss that compulsive behaviour as defined primarily from the perspective of animal experimentation falls short of the clinical phenomena and their neurobiological correlates. Thus for the human condition, the concept of compulsive habbits should be critically addressed and potentially revised.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13379","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140537791","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":"An epigenetic candidate–gene association study of parental styles in suicide attempters with substance use disorders","authors":"Clara Chrétienneau,&nbsp;Leticia M. Spindola,&nbsp;Florence Vorspan,&nbsp;Trine Vik Lagerberg,&nbsp;Cynthia Marie-Claire,&nbsp;Frank Bellivier,&nbsp;Stéphane Mouly,&nbsp;Jean-Louis Laplanche,&nbsp;Vanessa Bloch,&nbsp;Stéphanie Le Hellard,&nbsp;Romain Icick","doi":"10.1111/adb.13392","DOIUrl":"https://doi.org/10.1111/adb.13392","url":null,"abstract":"<p>Suicide attempts (SA) are prevalent in substance use disorders (SUD). Epigenetic mechanisms may play a pivotal role in the molecular mechanisms of environmental effects eliciting suicidal behaviour in this population. Hypothalamic–pituitary–adrenal axis (HPA), oxytocin and neurotrophin pathways have been consistently involved in SA, yet , their interplay with childhood adversity remains unclear, particularly in SUD. In 24 outpatients with SUDs, we examined the relation between three parental dysfunctional styles and history of SA with methylation of 32 genes from these pathways, eventually analysing 823 methylation sites. Extensive phenotypic characterization was obtained using a semi-structured interview. Parental style was patient-reported using the Measure of Parental Style (MOPS) questionnaire, analysed with and without imputation of missing items. Linear regressions were performed to adjust for possible confounders, followed by multiple testing correction. We describe both differentially methylated probes (DMPs) and regions (DMRs) for each set of analyses (with and without imputation of MOPS items). Without imputation, five DMRs in <i>OXTR</i>, <i>CRH</i> and <i>NTF3</i> significantly interacted with MOPS father abuse to increase the risk for lifetime SA, thus covering the three pathways. After imputation of missing MOPS items, two other DMPs from <i>FKBP5</i> and <i>SOCS3</i> significantly interacted with each of the three father styles to increase the risk for SA. Although our findings must be interpreted with caution due to small sample size, they suggest implications of stress reactivity genes in the suicidal risk of SUD patients and highlight the significance of father dysfunction as a potential marker of childhood adversity in SUD patients.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13392","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140343002","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":"Video game addiction is associated with early stage of inhibitory control problems: An event-related potential study using cued Go/NoGo task","authors":"Mazyar Fathi,&nbsp;Ali Mohammad Pourrahimi,&nbsp;Ahmad Poormohammad,&nbsp;Sara Sardari,&nbsp;Mohammad Amin Rajizadeh,&nbsp;Shahrzad Mazhari,&nbsp;Donya Pourkand","doi":"10.1111/adb.13391","DOIUrl":"https://doi.org/10.1111/adb.13391","url":null,"abstract":"<p>Video game addiction (VGA) is associated with cognitive problems, particularly deficits in inhibitory control. The present study aimed to investigate behavioural responses and event-related potential associated with specific response inhibition using the cued Go/NoGo task to examine the effects of VGA on brain activity related to response inhibition. Twenty-five individuals addicted to video games (action video games) and 25 matched healthy controls participated in the study. The results showed that the VGA group had significantly more commission error in the NoGo trials and faster reaction time in the Go trials compared with the control group. The event-related potential analyses revealed significant reductions in amplitudes of N2 cue and N2 NoGo in the VGA group. While there was no significant difference between the N2 amplitudes of the Go and NoGo trials in the VGA group, the control group had a larger N2 amplitude in the NoGo trials. These results indicate that VGA subjects have difficulties in the early stages of response inhibition, as well as some level of impairment in proactive cognitive control.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13391","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140343017","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":"Increased ventral anterior insular connectivity to sports betting availability indexes problem gambling","authors":"Damien Brevers,&nbsp;Chris Baeken,&nbsp;Antoine Bechara,&nbsp;Qinghua He,&nbsp;Pierre Maurage,&nbsp;Guillaume Sescousse,&nbsp;Claus Vögele,&nbsp;Joël Billieux","doi":"10.1111/adb.13389","DOIUrl":"10.1111/adb.13389","url":null,"abstract":"<p>With the advent of digital technologies, online sports betting is spurring a fast-growing expansion. In this study, we examined how sports betting availability modulates the brain connectivity of frequent sports bettors with [problem bettors (PB)] or without [non-problem bettors (NPB)] problematic sports betting. We conducted functional connectivity analyses centred on the ventral anterior insular cortex (vAI), a brain region playing a key role in the dynamic interplay between reward-based processes. We re-analysed a dataset on sports betting availability undertaken in PB (<i>n</i> = 30) and NPB (<i>n</i> = 35). Across all participants, we observed that sports betting availability elicited positive vAI coupling with extended clusters of brain activation (encompassing the putamen, cerebellum, occipital, temporal, precentral and central operculum regions) and negative vAI coupling with the orbitofrontal cortex. Between-group analyses showed increased positive vAI coupling in the PB group, as compared with the NPB group, in the left lateral occipital cortex, extending to the left inferior frontal gyrus, the anterior cingulate gyrus and the right frontal pole. Taken together, these results are in line with the central assumptions of triadic models of addictions, which posit that the insular cortex plays a pivotal role in promoting the drive and motivation to get a reward by ‘hijacking’ goal-oriented processes toward addiction-related cues. Taken together, these findings showed that vAI functional connectivity is sensitive not only to gambling availability but also to the status of problematic sport betting.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13389","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186088","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":"Conditioned morphine tolerance promotes neurogenesis, dendritic remodelling and pro-plasticity molecules in the adult rat hippocampus","authors":"Ghazaleh Ghamkhari Nejad,&nbsp;Francesca Mottarlini,&nbsp;Zohreh Tavassoli,&nbsp;Lucia Caffino,&nbsp;Fabio Fumagalli,&nbsp;Judith R. Homberg,&nbsp;Yaghoub Fathollahi","doi":"10.1111/adb.13377","DOIUrl":"https://doi.org/10.1111/adb.13377","url":null,"abstract":"<p>Structural neuroplasticity of the hippocampus in the form of neurogenesis and dendritic remodelling underlying morphine tolerance is still less known. Therefore, in this study, we aimed to assess whether unconditioned- and conditioned-morphine tolerance can trigger structural neuroplasticity in the dorsal and ventral parts of the adult male rat hippocampus. Evaluation of the levels of neurogenesis markers (Ki67 and DCX) by immunohistochemistry shows that conditioned morphine tolerance is sufficient to increase the baseline topographic level of hippocampal neurogenesis in adult rats. Dendritic spine visualization by Golgi staining shows that the behavioural testing paradigms themselves are sufficient to trigger the hippocampus subregion-specific changes in the dendritic remodelling along the apical dendrites of hippocampal CA1 pyramidal neurons and dentate granule cells in adult rats. Quantitative reverse transcription polymerase chain reaction of <i>Bdnf</i>, <i>Trkb</i>, <i>Rac-1</i> and <i>RhoA</i> mRNA levels as pro-plasticity molecules, shows that the conditioned morphine tolerance is effective in changing <i>Bdnf</i> and <i>RhoA</i> mRNA levels in the ventral hippocampus of adult rats. In summary, we demonstrate that the acquisition of morphine tolerance promotes adult neurogenesis, dendritic remodelling and pro-plasticity molecules such as <i>Bdnf/Trkb</i> in the rat hippocampus. Indeed, the structural neuroplasticity of the hippocampus may underlie the newly formed aberrant memory and could provide the initial basis for understanding the neurobiological mechanisms of morphine-tolerance plasticity in the hippocampus.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13377","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140164449","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":"Sex differences in heart rate variability measures that predict alcohol drinking in rats","authors":"Raizel M. Frasier,&nbsp;Phillip A. Starski,&nbsp;Thatiane de Oliveira Sergio,&nbsp;Angela J. Grippo,&nbsp;F. Woodward Hopf","doi":"10.1111/adb.13387","DOIUrl":"10.1111/adb.13387","url":null,"abstract":"<p>Problem alcohol drinking continues to be a substantial cost and burden. In addition, alcohol consumption in women has increased in recent decades, and women can have greater alcohol problems and comorbidities. Thus, there is a significant need for novel therapeutics to enhance sex-specific, individualized treatment. Heart rate (HR) and HR variability (HRV) are of broad interest because they may be both biomarkers for and drivers of pathological states. HRV reflects the dynamic balance between sympathetic (SNS, ‘fight or flight’) and parasympathetic (PNS, ‘rest and digest’) systems. Evidence from human studies suggest PNS predominance in women and SNS in men during autonomic regulation, indicating the possibility of sex differences in risk factors and physiological drivers of problem drinking. To better understand the association between HRV sex differences and alcohol drinking, we examined whether alcohol consumption levels correlated with time domain HRV measures (SDNN and rMSSD) at baseline, at alcohol drinking onset, and across 10 min of drinking, in adult female and male Wistar rats. In particular, we compared both HRV and HR measures under alcohol-only and compulsion-like conditions (alcohol + 10 mg/L quinine), because compulsion can often be a significant barrier to treatment of alcohol misuse. Importantly, previous work supports the possibility that different HRV measures could be interpreted to reflect PNS versus SNS influences. Here, we show that females with higher putative PNS indicators at baseline and at drinking onset had greater alcohol consumption. In contrast, male intake levels related to increased potential SNS measures at drinking onset. Once alcohol was consumed, HR predicted intake level in females, perhaps a pharmacological effect of alcohol. However, HRV changes were greater during compulsion-like intake versus alcohol-only, suggesting HRV changes (reduced SNS in females, reduced PNS and increased HR in males) specifically related to aversion-resistant intake. We find novel and likely clinically relevant autonomic differences associated with biological sex and alcohol drinking, suggesting that different autonomic mechanisms may promote differing aspects of female and male alcohol consumption.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159350","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":"Brain-specific serine/threonine-protein kinase 1 is a substrate of protein kinase C epsilon involved in sex-specific ethanol and anxiety phenotypes","authors":"Michael P. Dugan,&nbsp;Rajani Maiya,&nbsp;Caleb Fleischer,&nbsp;Michal Bajo,&nbsp;Angela E. Snyder,&nbsp;Ashwin Koduri,&nbsp;Sathvik Srinivasan,&nbsp;Marisa Roberto,&nbsp;Robert O. Messing","doi":"10.1111/adb.13388","DOIUrl":"10.1111/adb.13388","url":null,"abstract":"<p>Protein kinase C epsilon (PKCε) regulates behavioural responses to ethanol and plays a role in anxiety-like behaviour, but knowledge is limited on downstream substrates of PKCε that contribute to these behaviours. We recently identified brain-specific serine/threonine-protein kinase 1 (BRSK1) as a substrate of PKCε. Here, we test the hypothesis that BRSK1 mediates responses to ethanol and anxiety-like behaviours that are also PKCε dependent. We used in vitro kinase assays to further validate BRSK1 as a substrate of PKCε and used <i>Brsk1</i>^{<i>−/−</i>} mice to assess the role of BRSK1 in ethanol- and anxiety-related behaviours and in physiological responses to ethanol. We found that BRSK1 is phosphorylated by PKCε at a residue identified in a chemical genetic screen of PKCε substrates in mouse brain. Like <i>Prkce</i>^−/− mice, male and female <i>Brsk1</i>^{<i>−/−</i>} mice were more sensitive than wild-type to the acute sedative-hypnotic effect of alcohol. Unlike <i>Prkce</i>^{<i>−/−</i>} mice, <i>Brsk1</i>^{<i>−/−</i>} mice responded like wild-type to ataxic doses of ethanol. Although in <i>Prkce</i>^−/− mice ethanol consumption and reward are reduced in both sexes, they were reduced only in female <i>Brsk1</i>^{<i>−/−</i>} mice. Ex vivo slice electrophysiology revealed that ethanol-induced facilitation of GABA release in the central amygdala was absent in male <i>Brsk1</i>^{<i>−/−</i>} mice similar to findings in male <i>Prkce</i>^−/− mice. Collectively, these results indicate that BRSK1 is a target of PKCε that mediates some PKCε-dependent responses to ethanol in a sex-specific manner and plays a role distinct from PKCε in anxiety-like behaviour.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"29 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.13388","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140144436","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}