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Dihydrotestosterone and Finasteride Effects on Alcohol Cue-Elicited Brain Activity in Males With Heavy Episodic Drinking 双氢睾酮和非那雄胺对酒精提示引起的间歇性重度饮酒男性大脑活动的影响。
IF 2.6 3区 医学
Addiction Biology Pub Date : 2026-01-28 DOI: 10.1111/adb.70123
Rafat Boroumand-Jazi, Sabine Hoffmann, Iris Reinhard, Patrick Bach, Wolfgang H. Sommer, Marlene Kundlacz, Christian P. Müller, Matthias Reichl, Haoye Tan, Leonard P. Wenger, Anne Beck, Sabine Vollstädt-Klein, Falk Kiefer, Christiane Mühle, Sarah Gerhardt, Bernd Lenz
{"title":"Dihydrotestosterone and Finasteride Effects on Alcohol Cue-Elicited Brain Activity in Males With Heavy Episodic Drinking","authors":"Rafat Boroumand-Jazi,&nbsp;Sabine Hoffmann,&nbsp;Iris Reinhard,&nbsp;Patrick Bach,&nbsp;Wolfgang H. Sommer,&nbsp;Marlene Kundlacz,&nbsp;Christian P. Müller,&nbsp;Matthias Reichl,&nbsp;Haoye Tan,&nbsp;Leonard P. Wenger,&nbsp;Anne Beck,&nbsp;Sabine Vollstädt-Klein,&nbsp;Falk Kiefer,&nbsp;Christiane Mühle,&nbsp;Sarah Gerhardt,&nbsp;Bernd Lenz","doi":"10.1111/adb.70123","DOIUrl":"10.1111/adb.70123","url":null,"abstract":"<p>Preliminary animal and human studies have shown that blood dihydrotestosterone concentrations are increased in males with alcohol use disorder, and 5α-reductase inhibitors, which decrease dihydrotestosterone concentrations, reduce alcohol consumption. To gain mechanistic insight, we studied the effects of reduced dihydrotestosterone concentrations following pharmacological 5α-reductase inhibition on alcohol cue-elicited brain activity and alcohol craving in males with problematic alcohol use. To this end, this randomized, placebo-controlled, crossover challenge experiment investigated associations between dihydrotestosterone concentrations and brain functional magnetic resonance imaging (fMRI) activity during exposure to visual alcohol cues and alcohol craving following a single dose of 5 mg finasteride versus placebo in 50 males with heavy episodic drinking. We used finasteride because it specifically inhibits 5α-reductase II activity, which is the main enzyme converting testosterone to dihydrotestosterone. Dihydrotestosterone concentrations were lower in the finasteride condition in comparison to the placebo condition, but not significantly associated with brain activation patterns or craving. In the exploratory analyses, we found higher brain activity during exposure to visual stimuli in the right and left caudate nuclei, the right superior frontal gyrus and the left insula in the finasteride condition versus the placebo condition. Moreover, finasteride versus placebo was associated with a higher wish to not drink alcohol. The results of this experimental study do not support the à priori hypothesis that dihydrotestosterone concentrations play a role in brain activation during exposure to visual alcohol cues, but indicate that finasteride effects may be mediated by other pathways. Future studies are requested to investigate the effects of reduced dihydrotestosterone concentrations over a longer time and to shed light on the molecular mechanisms underlying the here observed effects of finasteride.</p><p><b>Trial Registration:</b> DRKS00020569</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"31 2","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12848907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146067998","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}
引用次数: 0
CO2 Reactivity but Not CO2-Induced Orexin/c-Fos Colocalization Differentially Predicts Alcohol-Seeking Behaviour After Extinction and Retrieval-Extinction in Rats 二氧化碳反应性而非二氧化碳诱导的Orexin/c-Fos共定位差异预测大鼠在灭绝和检索-灭绝后的酒精寻求行为
IF 2.6 3区 医学
Addiction Biology Pub Date : 2026-01-22 DOI: 10.1111/adb.70116
Marissa Raskin, Marcelle Olvera, Kylee A. Smith, Roberto Cofresí, Jason Shumake, Michael J. Telch, Michael W. Otto, Jasper A. J. Smits, Rueben Gonzales, Hongjoo J. Lee, Marie-H. Monfils
{"title":"CO2 Reactivity but Not CO2-Induced Orexin/c-Fos Colocalization Differentially Predicts Alcohol-Seeking Behaviour After Extinction and Retrieval-Extinction in Rats","authors":"Marissa Raskin,&nbsp;Marcelle Olvera,&nbsp;Kylee A. Smith,&nbsp;Roberto Cofresí,&nbsp;Jason Shumake,&nbsp;Michael J. Telch,&nbsp;Michael W. Otto,&nbsp;Jasper A. J. Smits,&nbsp;Rueben Gonzales,&nbsp;Hongjoo J. Lee,&nbsp;Marie-H. Monfils","doi":"10.1111/adb.70116","DOIUrl":"10.1111/adb.70116","url":null,"abstract":"<p>Cues associated with alcohol consumption can trigger cravings, seeking behaviour and relapse after abstinence in individuals with alcohol use disorder (AUD). These conditioned responses can be attenuated through extinction learning, a core component of cue exposure therapy (CET). CET is effective in some individuals with AUD but not all, so it is necessary to develop strategies to identify and intervene with individuals unlikely to benefit from CET. Another method for attenuating conditioned responding is retrieval-extinction, which renders the original associative memory labile via distinct neural mechanisms. We recently demonstrated that CO<sub>2</sub> reactivity predicts extinction memory for both fear and food cues, and fear memory after retrieval-extinction, and CO<sub>2</sub>-induced orexin/c-Fos colocalization predicts fear extinction memory. The purpose of the current study was to examine whether the predictive power of CO<sub>2</sub> reactivity might extend to alcohol-seeking behaviour after extinction or retrieval-extinction in male and female rats. We also examined the relationship between CO<sub>2</sub> reactivity, return of alcohol-seeking behaviour and CO<sub>2</sub>-induced orexin/c-Fos colocalization. Male and female rats first underwent alcohol drinking induction in the homecage followed by dependence via exposure to chronic intermittent ethanol vapour or control air and homecage drinking. All rats then underwent Pavlovian alcohol conditioning followed by either standard extinction or retrieval-extinction. They then received a long-term memory (LTM) test and CO<sub>2</sub> challenge followed by euthanasia for brain harvesting. CO<sub>2</sub> reactivity differentially predicted LTM after extinction and retrieval-extinction. There were no relationships between orexin/c-Fos colocalization and CO<sub>2</sub> reactivity or LTM. The predictive power of CO<sub>2</sub> reactivity extends to alcohol-seeking behaviour after extinction and retrieval-extinction in alcohol dependent and nondependent male and female rats, while its relationship with orexin/c-Fos colocalization does not. CO<sub>2</sub> reactivity could be used as a screening tool to determine whether an individual may be a good candidate for CET or a retrieval-extinction–based approach.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"31 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12824593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020290","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}
引用次数: 0
Association Between Heroin Use and Depression: NHANES 2005–2018 海洛因使用与抑郁症之间的关系:NHANES 2005-2018。
IF 2.6 3区 医学
Addiction Biology Pub Date : 2026-01-21 DOI: 10.1111/adb.70127
Bei Li, Zhuojun Yang, Xiaoxiao Zhang, Mei Yang, Hong Qiu, Yulan Ren
{"title":"Association Between Heroin Use and Depression: NHANES 2005–2018","authors":"Bei Li,&nbsp;Zhuojun Yang,&nbsp;Xiaoxiao Zhang,&nbsp;Mei Yang,&nbsp;Hong Qiu,&nbsp;Yulan Ren","doi":"10.1111/adb.70127","DOIUrl":"10.1111/adb.70127","url":null,"abstract":"<p>Heroin use and major depression are each leading contributors to global disability and premature mortality, yet evidence for a specific association between the two remains fragmented and is often derived from small, treatment-seeking samples. We conducted a cross-sectional analysis of nationally representative data from the 2005–2018 National Health and Nutrition Examination Survey, including 19 022 US adults aged ≥ 20 years with complete information on heroin use, depression status, and relevant covariates. Clinically significant depression was defined as a PHQ-9 score ≥ 10. After multivariable adjustment for sociodemographic, behavioural, and clinical factors, including polysubstance use and chronic medical conditions, lifetime heroin use was independently associated with depression (adjusted OR = 1.85, 95% CI 1.43–2.40; <i>p</i> &lt; 0.001). Subgroup analyses demonstrated that this association was robust and modified by age and smoking status, with significant interaction effects observed (<i>p</i> for interaction &lt; 0.05). Restricted cubic spline analysis among participants with a history of heroin use (<i>n</i> = 439) revealed a non-linear relationship between age at first heroin use and depression risk (<i>p</i> for non-linearity = 0.032), with the highest predicted probability of depression among individuals who initiated use at or before 20.4 years of age. These findings indicate that lifetime heroin use is associated with a substantially increased risk of clinically significant depression in the general US population, particularly among younger adults and current smokers, underscoring the need for integrated screening and concurrent treatment of substance-use and mood disorders.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"31 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12820517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146012957","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}
引用次数: 0
Optimizing Control Definitions in Opioid Use Disorder Genetic Research Using Electronic Health Records 利用电子健康记录优化阿片类药物使用障碍遗传研究中的控制定义。
IF 2.6 3区 医学
Addiction Biology Pub Date : 2026-01-19 DOI: 10.1111/adb.70094
Maria Niarchou, Ellen L. Tsai, Mariela V. Jennings, Annika Faucon, Hyunjoon Lee, Kritika Singh, Justin D. Tubbs, Panos Roussos, Tian Ge, Richard C. Crist, Rachel Vickers-Smith, Howard Edenberg, Amy Moore, Bradley T. Webb, Eric O. Johnson, PsycheMERGE Substance Use Disorder Workgroup, Rachel L. Kember, Jordan W. Smoller, Lea K. Davis, Brandon J. Coombes, Georgios Voloudakis, David Burstein, Travis T. Mallard, Vanessa Troiani, Sandra Sanchez-Roige
{"title":"Optimizing Control Definitions in Opioid Use Disorder Genetic Research Using Electronic Health Records","authors":"Maria Niarchou,&nbsp;Ellen L. Tsai,&nbsp;Mariela V. Jennings,&nbsp;Annika Faucon,&nbsp;Hyunjoon Lee,&nbsp;Kritika Singh,&nbsp;Justin D. Tubbs,&nbsp;Panos Roussos,&nbsp;Tian Ge,&nbsp;Richard C. Crist,&nbsp;Rachel Vickers-Smith,&nbsp;Howard Edenberg,&nbsp;Amy Moore,&nbsp;Bradley T. Webb,&nbsp;Eric O. Johnson,&nbsp;PsycheMERGE Substance Use Disorder Workgroup,&nbsp;Rachel L. Kember,&nbsp;Jordan W. Smoller,&nbsp;Lea K. Davis,&nbsp;Brandon J. Coombes,&nbsp;Georgios Voloudakis,&nbsp;David Burstein,&nbsp;Travis T. Mallard,&nbsp;Vanessa Troiani,&nbsp;Sandra Sanchez-Roige","doi":"10.1111/adb.70094","DOIUrl":"10.1111/adb.70094","url":null,"abstract":"<p>Amidst the opioid crisis, understanding the genetic basis of opioid use disorder (OUD) is crucial for identifying biological mechanisms and intervention points. However, genome-wide association studies (GWASs) have been hampered by inadequate sample sizes and often the use of control populations not assessed for prior opioid exposure. Because opioid exposure is a prerequisite for the development of OUD, consideration of exposure history in controls is important. Electronic health record data (EHR) paired with genomic information allow a broader sampling of patients with OUD and exposed controls. We leveraged data across two healthcare systems to evaluate the impact of using controls not screened for opioid exposure (‘generic’) versus minimally opioid-exposed control (‘exposed’). First, at the phenotypic level, we conducted phenome-wide association studies (PheWAS) to compare the medical comorbidity profiles of OUD cases when using generic versus exposed controls. While PheWAS results for OUD-related comorbidities were more pronounced when using the generic group, 83% of the disease associations were overlapping and of similar effect sizes. Second, at the genetic level, we conducted GWAS (cases vs. generic; cases vs. exposed) and assessed differences in genetic correlations and degrees of phenotypic misclassification. Genetic results were concordant across control groups based on heritability (generic: 0.16 ± 0.07 vs. 0.10 ± 0.07), associations with the coding <i>OPRM1</i> variant rs1799971 (<i>p</i><sub><i>generic</i></sub> = 8.83E-03 vs. <i>p</i><sub><i>exposed</i></sub> = 1.83E-02) and genetic correlations with prior OUD GWAS (<i>r</i><sub><i>g-generic</i></sub> = 0.83 ± 0.26 vs. <i>r</i><sub><i>g-exposed</i></sub> = 0.78 ± 0.27). Although GWASs were limited by sample size (<i>N</i><sub>generic</sub> = 6269, <i>N</i><sub>exposed</sub> = 6365), compared to an independent OUD GWAS (<i>N</i> = 425 944), the dilution value for the two GWAS was not different from 1, suggesting no major impact of phenotypic misclassification. This study represents the first effort to enhance OUD genetic research through optimization of control definitions using EHR data. Generic controls ascertained within the US health systems, where exposure to prescription opioids is high, offer a practical alternative for genetic studies of OUD.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"31 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70094","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145999410","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}
引用次数: 0
Activation of Insula-Accumbal Projection Neurons Is Required for Relapse-Like Behaviour Following Opioid Self-Administration 阿片类药物自我给药后复发样行为需要激活岛伏隔投射神经元。
IF 2.6 3区 医学
Addiction Biology Pub Date : 2026-01-12 DOI: 10.1111/adb.70118
Rachel E. Clarke, Bayleigh E. Pagoota, Isabella E. Dinu, Jacqueline E. Paniccia, Anna C. Tsyrulnikov, Annaka M. Westphal, Jade Baek, Michael D. Scofield, James M. Otis
{"title":"Activation of Insula-Accumbal Projection Neurons Is Required for Relapse-Like Behaviour Following Opioid Self-Administration","authors":"Rachel E. Clarke,&nbsp;Bayleigh E. Pagoota,&nbsp;Isabella E. Dinu,&nbsp;Jacqueline E. Paniccia,&nbsp;Anna C. Tsyrulnikov,&nbsp;Annaka M. Westphal,&nbsp;Jade Baek,&nbsp;Michael D. Scofield,&nbsp;James M. Otis","doi":"10.1111/adb.70118","DOIUrl":"10.1111/adb.70118","url":null,"abstract":"<p>The insular cortex (IC) is known to underlie drug seeking and relapse for multiple drug classes, yet the precise role the IC plays in opioid use disorder (OUD) remains unclear. In preclinical models of OUD, inhibition of the IC has produced conflicting results, such that in some cases the IC seems to promote opioid seeking whereas in others the IC seems to blunt opioid seeking. These results may be related to the heterogeneity of cortical output circuits, which can have opposing functions despite their relative proximity. Thus, here we examined the role of a specific IC output circuit, from the anterior IC (aIC) to the nucleus accumbens core (NAcc), for opioid seeking. We find in mice that following 14 days of heroin self-administration and 3 days of forced abstinence, optogenetic inhibition of aIC➔NAcc terminals suppresses context-associated opioid seeking. Furthermore, the same manipulation attenuates cued opioid seeking following extinction training. Importantly, we observed no effect of aIC➔NAcc terminal inhibition on sucrose seeking. Together, our results reveal that the IC selectively controls opioid seeking through a discrete population of NAcc projecting neurons, providing the first evidence for a projection-specific role of IC circuitry in opioid seeking and relapse.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"31 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70118","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145960566","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}
引用次数: 0
Neural Response to Theta-Burst Stimulation Predicts Long-Term Relapse in Patients With Alcohol Use Disorder: A Pilot fMRI Study 神经对θ -爆发刺激的反应预测酒精使用障碍患者的长期复发:一项先导功能磁共振成像研究
IF 2.6 3区 医学
Addiction Biology Pub Date : 2026-01-11 DOI: 10.1111/adb.70109
Jing-Nan Zhao, Chu-Yue Zhao, Ying-Ying Li, Li-Ping Liu, Zhi-Jun Liu
{"title":"Neural Response to Theta-Burst Stimulation Predicts Long-Term Relapse in Patients With Alcohol Use Disorder: A Pilot fMRI Study","authors":"Jing-Nan Zhao,&nbsp;Chu-Yue Zhao,&nbsp;Ying-Ying Li,&nbsp;Li-Ping Liu,&nbsp;Zhi-Jun Liu","doi":"10.1111/adb.70109","DOIUrl":"10.1111/adb.70109","url":null,"abstract":"<p>Alcohol use disorder (AUD) is characterized by high relapse rates, and relapse is often driven by cue-induced cravings linked to prefrontal–subcortical network dysregulation. This study investigated the neurobiological effects of inhibitory continuous theta-burst stimulation (cTBS) targeting the right dorsolateral prefrontal cortex (rDLPFC) in patients with AUD. In a randomized, double-blind, sham-controlled trial, 28 patients (16 in the active cTBS group and 12 patients in the sham group) underwent 10 sessions of rDLPFC-cTBS. fMRI was performed before and after intervention to assess neural responses to alcohol cues, and relapse was monitored for 1 year. The active cTBS group exhibited a significantly lower relapse risk over the 12-month follow-up compared to the sham group (HR = 0.210, 95% CI [0.070, 0.633]). A significant group-by-intervention interaction was found in the right superior frontal gyrus (<i>p</i> = 0.047); active cTBS prevented the cue-induced hyperactivity that was observed in the sham group, suggesting a network stabilization effect. Furthermore, a machine learning model that was trained on intervention-induced changes in brain-wide neural activity accurately predicted long-term relapse (accuracy: 78.7%; AUC: 0.903). Increased postintervention reactivity to cues in the left medial prefrontal cortex was the strongest predictor of relapse. These findings demonstrate that rDLPFC-cTBS modulates craving-related circuits and that the dynamic neural response to treatment is a powerful biomarker for predicting relapse; the findings pave the way for the development of personalized addiction medicine.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"31 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12791151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145953522","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}
引用次数: 0
Letter to the Editor: Dopamine D2S/D2L Receptor Regulation of Alcohol-Induced Reward and Signalling 致编辑的信:多巴胺D2S/D2L受体对酒精诱导的奖赏和信号传导的调节。
IF 2.6 3区 医学
Addiction Biology Pub Date : 2026-01-08 DOI: 10.1111/adb.70117
Mohsin Tariq, Muhammad Ahmad, Mian Zain Hayat, Meer Hassan Khalid
{"title":"Letter to the Editor: Dopamine D2S/D2L Receptor Regulation of Alcohol-Induced Reward and Signalling","authors":"Mohsin Tariq,&nbsp;Muhammad Ahmad,&nbsp;Mian Zain Hayat,&nbsp;Meer Hassan Khalid","doi":"10.1111/adb.70117","DOIUrl":"10.1111/adb.70117","url":null,"abstract":"&lt;p&gt;I would like to commend Tayyab et al. [&lt;span&gt;1&lt;/span&gt;] for their innovative and mechanistically rich investigation into the differential roles of D2S and D2L dopamine receptor isoforms in alcohol-induced reward and intracellular signalling. Their work provides an important contribution to addiction neuroscience by dissecting isoform-specific pathways that have historically been difficult to resolve using conventional pharmacological approaches. The study's integration of behavioural, molecular and receptor-specific knockout strategies offers valuable insights into how distinct D2 receptor subtypes contribute to alcohol-associated reinforcement. However, certain methodological and interpretative aspects warrant further discussion to strengthen the translational significance of these findings.&lt;/p&gt;&lt;p&gt;First, although the authors elegantly demonstrate isoform-specific effects, the behavioural paradigms used including conditioned place preference (CPP) are susceptible to variability in motivational salience among rodents. For instance, prior work by Cunningham et al. [&lt;span&gt;2&lt;/span&gt;] highlighted how environmental and handling factors significantly modulate CPP outcomes, suggesting that additional behavioural assays such as operant self-administration may have enhanced robustness and reproducibility.&lt;/p&gt;&lt;p&gt;Second, the study's signalling analyses focus primarily on Akt/GSK3β and ERK pathways. While these are well-established downstream targets of D2 receptors, they do not fully capture the complex signalling landscape implicated in alcohol reward. For instance, Beaulieu et al. [&lt;span&gt;3&lt;/span&gt;] demonstrated that D2 receptor signalling involves β-arrestin–dependent cascades that may diverge between D2S and D2L isoforms. Inclusion of such pathways would enhance mechanistic depth and clarify potential isoform-specific signalling bifurcations.&lt;/p&gt;&lt;p&gt;Third, although the authors utilized D2S- and D2L-specific knockout mice, developmental compensation remains a potential confound. For instance, as noted by Kelly et al. [&lt;span&gt;4&lt;/span&gt;], constitutive deletion of dopamine receptor variants can lead to homeostatic rewiring of dopaminergic circuitry, potentially obscuring acute isoform contributions. Conditional or inducible knockout models could help mitigate these confounds and improve mechanistic precision.&lt;/p&gt;&lt;p&gt;Lastly, while the study compellingly links D2S to enhanced alcohol reward, long-term neuroadaptive changes were not explored. For instance, Koob and Volkow [&lt;span&gt;5&lt;/span&gt;] emphasized that addiction is driven by progressive transitions in reward, stress and executive control circuits. Longitudinal or chronic-exposure models would therefore help determine whether D2 isoform-specific signalling contributes to long-term vulnerability rather than acute reward alone.&lt;/p&gt;&lt;p&gt;Future investigations should consider integrating multi-modal behavioural paradigms, β-arrestin pathway analyses, inducible genetic models and long-term neuroadaptation studies to expand","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"31 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12783058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145935706","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}
引用次数: 0
The Selective Bromodomain and Extra-Terminal Domain (BET) Inhibitor RVX-208 Reduces Cocaine-Seeking Behaviour and Alters Proteomic Pathways in the Nucleus Accumbens 选择性溴域和外端结构域(BET)抑制剂RVX-208减少伏隔核的可卡因寻找行为并改变蛋白质组学途径。
IF 2.6 3区 医学
Addiction Biology Pub Date : 2026-01-08 DOI: 10.1111/adb.70121
Tyler J. Sacko, Afshin Seyednejad, Jesse Engelhardt, Gregory C. Sartor
{"title":"The Selective Bromodomain and Extra-Terminal Domain (BET) Inhibitor RVX-208 Reduces Cocaine-Seeking Behaviour and Alters Proteomic Pathways in the Nucleus Accumbens","authors":"Tyler J. Sacko,&nbsp;Afshin Seyednejad,&nbsp;Jesse Engelhardt,&nbsp;Gregory C. Sartor","doi":"10.1111/adb.70121","DOIUrl":"10.1111/adb.70121","url":null,"abstract":"<p>Bromodomain and extra terminal domain (BET) epigenetic ‘reader’ proteins are key regulators of both behavioural and molecular responses to cocaine. In substance use disorder (SUD) models, BET function has primarily been investigated using small molecule inhibitors that prevent both bromodomains of BET proteins from interacting with acetylated histones. Although these inhibitors have been shown to be effective in SUD models, the potential adverse effects of pan-BET inhibition may restrict translational applications. Recently, RVX-208, a clinically tested and domain-selective BET inhibitor, was found to reduce cocaine conditioned responses and cocaine-induced gene expression in the nucleus accumbens (NAc), while avoiding the learning and memory impairments associated with pan-BET inhibitors. However, the effectiveness of RVX-208 in cocaine self-administration procedures remains unclear. Here, we investigated whether repeated RVX-208 treatment during abstinence altered cocaine-seeking behaviour in rats trained to self-administer cocaine. Male and female Sprague Dawley rats underwent 17 days of cocaine or sucrose self-administration, followed by daily treatment with vehicle or RVX-208 (25 mg/kg, ip) during a 14-day abstinence period. Rats in the RVX-208-treated group showed reduced lever pressing compared to vehicle controls. Sucrose-seeking and open field behaviour (distance travelled and time in the centre zone) were not significantly affected by RVX-208 treatment. Proteomic analysis of the NAc revealed that RVX-208 modulated several proteins, including those associated with dopamine activity (DRD1 and SLC6A3), transcriptional regulation (NFKB1), glutamate transport (SLC1A2) and ion channel activity (KCNJ10), and many changes were sex-dependent. Collectively, these findings indicate that domain-selective BET inhibition is effective at reducing cocaine-seeking behaviour and point to novel mechanisms that may contribute to its therapeutic effect.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"31 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12783071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145935713","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}
引用次数: 0
Associations Between Vitamin D Status and Clinical Presentation Among French Inpatients With Substance Use Disorders 法国物质使用障碍住院患者维生素D状况与临床表现之间的关系
IF 2.6 3区 医学
Addiction Biology Pub Date : 2026-01-08 DOI: 10.1111/adb.70110
Luca Pavirani, Bibi Aliya Seelarbokus, Léa Marinelli, Pauline Desnavailles, Sylvie Berthoz, Melina Fatseas
{"title":"Associations Between Vitamin D Status and Clinical Presentation Among French Inpatients With Substance Use Disorders","authors":"Luca Pavirani,&nbsp;Bibi Aliya Seelarbokus,&nbsp;Léa Marinelli,&nbsp;Pauline Desnavailles,&nbsp;Sylvie Berthoz,&nbsp;Melina Fatseas","doi":"10.1111/adb.70110","DOIUrl":"10.1111/adb.70110","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Numerous studies have demonstrated that vitamin D plays a crucial role in modulating dopaminergic pathways, suggesting a potential role in the pathophysiology of addictive disorders. However, among individuals with substance use disorders (SUDs), the link between vitamin D and addiction-related symptoms has not been sufficiently studied.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aims to explore among inpatients treated for various types of SUDs differences in addiction-related, psychopathological and biological characteristics based on vitamin D status.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The sample included 260 participants hospitalized in a French addiction treatment unit. Vitamin D concentration and other biomarkers, SUDs severity and other psychiatric disorders, cognitive functioning and impulsivity were collected at hospital admission (T0). Perceived negative affectivity and craving (for the main substance and food) were collected at T0 and hospital discharge (T1).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>About 89.3% of the participants had a vitamin D deficiency as defined by French recommendations (&lt; 30 ng/mL). Using univariate between-group analyses, vitamin D deficiency was associated with higher body weight and lower calcium plasma levels at T0, as well as increased craving intensity for both the substance at the origin of the treatment and food at T1. Multivariate regression analyses showed no significant associations between vitamin D or calcium levels and craving intensities at T1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study confirms the high prevalence of vitamin D deficiency among inpatients treated for SUDs. Although preliminary, our findings highlight the importance of assessing vitamin D levels in SUDs. They call for further research on its role in relapse vulnerability and the potential benefits of its supplementation during drug withdrawal treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"31 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918664","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}
引用次数: 0
The Role of the Posterior Paraventricular Nucleus of the Thalamus in Food Deprivation-Induced Heroin-Seeking Relapse, in Male and Female Rats 在雄性和雌性大鼠中,丘脑室旁后核在食物剥夺诱导的海洛因寻求复发中的作用
IF 2.6 3区 医学
Addiction Biology Pub Date : 2026-01-08 DOI: 10.1111/adb.70115
Catarina Borges, Anita Darecka, Amélie Mainville-Berthiaume, Emily Ah-Yen, Mahgol Darvishmolla, Richard Courtemanche, Uri Shalev
{"title":"The Role of the Posterior Paraventricular Nucleus of the Thalamus in Food Deprivation-Induced Heroin-Seeking Relapse, in Male and Female Rats","authors":"Catarina Borges,&nbsp;Anita Darecka,&nbsp;Amélie Mainville-Berthiaume,&nbsp;Emily Ah-Yen,&nbsp;Mahgol Darvishmolla,&nbsp;Richard Courtemanche,&nbsp;Uri Shalev","doi":"10.1111/adb.70115","DOIUrl":"https://doi.org/10.1111/adb.70115","url":null,"abstract":"<p>Abstinence from drug use is often the result of the associated negative consequences. However, relapse occurs in a large proportion of abstinent users, and the underlying brain mechanisms are not clear. An arguably relevant brain area is the posterior paraventricular nucleus of the thalamus (pPVT), which plays a role in motivational processes and addiction-like behaviours. Using a punishment-imposed abstinence procedure, we assessed the effect of chemogenetic inhibition and excitation of the pPVT on food deprivation-induced relapse to heroin-seeking in male and female rats. Rats were trained to self-administer heroin (0.1 mg/kg/infusion) for 2 weeks under a seeking–taking chain schedule. For punishment-imposed abstinence, a mild footshock (0.2 to 0.6 mA) was delivered on 30% of the completed seek lever links instead of access to the take lever. Relapse to heroin-seeking was tested after 24 h of food deprivation and under sated condition. Animals were injected (i.p.) with either a DREADD ligand or vehicle 15–20 min before the tests. There was no sex difference in heroin self-administration or punishment-imposed abstinence. Under the food deprivation condition, chemogenetic inhibition of the pPVT increased heroin-seeking compared to the control group, only in male rats. Chemogenetic excitation of the pPVT resulted in an increase in heroin-seeking under food deprivation conditions. Our results support an involvement of the pPVT in relapse to heroin-seeking and suggest a sex-dependent effect.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"31 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145930845","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}
引用次数: 0
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