Addiction Biology最新文献

{"title":"DNA Methylation Regulates CDK5R1 and NRBP1 to Exert Effects on Alcohol Dependence: Insights From Mendelian Randomization.","authors":"Fuyuan Deng, Junsheng Peng, Siran Lai, Guangpeng Zhang, Miaomiao Li, Yuxin Huang, Mi Yuan, Gaolei Yao, Peiming Zhang, Liming Lu","doi":"10.1111/adb.70162","DOIUrl":"https://doi.org/10.1111/adb.70162","url":null,"abstract":"<p><p>Alcohol dependence currently lacks targeted pharmacotherapies, underscoring the urgent need for novel therapeutic targets. Existing research on disease-associated DNA methylation changes and their gene regulatory effects remains inconsistent. To resolve this uncertainty, we applied the Mendelian randomization to elucidate causal mechanisms connecting druggable genes, epigenetic regulation and alcohol dependence development. Integrating MR, colocalization and mediation analyses, we leveraged genome-wide association study (GWAS) (FinnGen), eQTL (eQTLGen) and methylation (GoDMC) data. We assessed causal gene-alcohol dependence relationships, shared causal variants via colocalization and methylation-mediated regulatory mechanisms. Our integrative analysis identified 10 drug-targetable genes showing significant expression alterations in alcohol dependence (FDR < 0.05), with three genes (CDK5R1, CAMKK2 and NRBP1) demonstrating evidence of shared causal variants through colocalization. Epigenetic regulation was particularly evident at two methylation sites (cg07437263 and cg05102552) that indirectly influenced alcohol dependence risk by modulating CDK5R1 (63.92% mediation) and NRBP1 (95.12% mediation) expression. These findings reveal DNA methylation as a critical regulatory mechanism governing neuronal gene expression patterns in alcohol dependence pathogenesis. The strong mediation effects observed for CDK5R1 and NRBP1, coupled with their colocalization evidence, position these genes as promising candidates for both biomarker development and targeted therapeutic interventions in alcohol dependence. This investigation spotlights the regulatory function of DNA methylation on CDK5R1 and NRBP1 in alcohol dependence. It implies that CDK5R1 and NRBP1 could serve as potential clinical biomarkers or therapeutic targets for the early management of alcohol dependence.</p>","PeriodicalId":48966,"journal":{"name":"Addiction Biology","volume":"31 5","pages":"e70162"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13105825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147786360","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":"Longitudinal Study of Plasma NFL and GFAP as Biomarkers of Alcohol Withdrawal-Associated Brain Injury.","authors":"Virgile Clergue-Duval, Frank Questel, Alexandra Dereux, Elodie Bouaziz-Amar, Julien Azuar, Romain Icick, Dorian Rollet, Vanessa Bloch, Jérôme Jeanblanc, Cynthia Marie-Claire, Jean-Louis Laplanche, Frank Bellivier, Claire Paquet, Mickael Naassila, Florence Vorspan","doi":"10.1111/adb.70157","DOIUrl":"10.1111/adb.70157","url":null,"abstract":"<p><p>Plasma neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), tau protein and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) are candidate biomarkers of alcohol withdrawal (AW)-associated brain toxicity, as they are biomarkers of axonal, neuronal or glial injury. The aim of this study was to investigate the changes of these biomarkers during AW in patients with severe alcohol use disorder (AUD). Plasma NFL, GFAP, tau and UCHL1 levels were measured, with SIMOA, at three times: on Day 1 (T1), on Day 3 or 4 (T2) and on Day 13, 14 or 15 (T3) of AW. They were analysed with a linear mixed model adjusted for age, sex and body mass index. Changes in these levels according to AW symptom severity were evaluated. Twenty-four inpatients with severe AUD were included: 20 men (83.3%), aged 47.4 years [±11.3], with symptoms requiring a median equivalent-diazepam dose of 0.81 mg/kg at T1. A significant increase was observed for NFL level from T1 to T2 (β = 0.349, p = 0.035), but not for GFAP, tau or UCHL1 levels. In AW symptom severity analyses, a significant positive association was found with equivalent-diazepam dose required × T1-T2 time interaction factor for NFL (β = 0.161, p = 0.028) and for GFAP (β = 0.400, p = 9.9 × 10^-4). This longitudinal study provided preliminary indication that brain injury could occur within the first days of AW, especially in patients with severe pharmacological dependence. Plasma NFL and GFAP are promising biomarkers of AW-related brain pathology and should be investigated as biomarkers of therapeutic response to test innovative drug strategies for preventing this toxicity. Trial Registration: Clinical Trials: NCT05216705.</p>","PeriodicalId":48966,"journal":{"name":"Addiction Biology","volume":"31 5","pages":"e70157"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147822547","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":"Blood-Based Epigenetic Signatures in Brazilian Males With Alcohol Use Disorder.","authors":"Laís da Silva Pereira-Rufino, Raissa Mazzer de Sino Romano, Regiane Chiavelli Lamim, Rafael Conte, Denise Ribeiro Gobbo, Marcelo Carvalho da Conceição, Vanessa Kiyomi Ota, Lucas Liro, Leslie Domenici Kulikowsk, Adriana Marcassa Tucci, Ana Lucia de Moraes Horta, Ana Maria Sebastião, Maria Lucia Oliveira Souza-Formigoni, João Ricardo Nickenig Vissoci, Alexandre Ferro Aissa, Isabel Cristina Céspedes","doi":"10.1111/adb.70161","DOIUrl":"https://doi.org/10.1111/adb.70161","url":null,"abstract":"<p><p>Alcohol use disorder (AUD) is a chronic and progressive disease that affects individuals worldwide. AUD individuals exhibit epigenetic alterations across tissues, mainly in the brain. Despite advances in the field, there is a gap in epigenome-wide association studies (EWAS) conducted in a Brazilian cohort that is genetically and culturally diverse. This study aimed to describe an exploratory EWAS conducted in Brazilian males with AUD and to identify DNA methylation signatures associated with brain-related biological pathways. Peripheral blood samples were collected from 54 patients with AUD in the early stages of withdrawal (AUD group) and 70 control individuals (CON group) (Brazil, São Paulo). Genome-wide DNA methylation was assessed using the Infinium MethylationEPIC BeadChip v2.0. We identified four differentially methylated loci in genes involved in intracellular signalling and cellular stress responses. Focusing on the nervous system, enrichment analyses revealed pathways related to neuronal/axon development and synaptic organization hypomethylated in the AUD group (p. adjust < 0.05). Differentially methylated regions (DMRs) showed hypomethylation in regulatory and exonic regions of ABAT, DLX5, PHGDH, TRPM2 and GABBR1 genes, which are within the enriched pathways. In conclusion, to the best of our knowledge, this is the first EWAS in a Brazilian cohort with AUD to identify alterations in DNA methylation, highlighting genes and pathways involved in neurogenesis, synaptic and GABAergic signalling. These epigenetic modifications suggest an impact of chronic alcohol consumption on critical biological processes of the CNS, potentially contributing to the cognitive and behavioural impairments observed in AUD. The results reinforce the importance of epigenetic studies in mixed-race populations.</p>","PeriodicalId":48966,"journal":{"name":"Addiction Biology","volume":"31 5","pages":"e70161"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13122561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147786381","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":"Virtual Reality-Based Cue Exposure and Aversion Therapy for Alcohol Dependence: A Randomized Controlled Trial.","authors":"Haoyu Zhao, Xiaotong Ying, Xiaoyu Du, Genhui Ren, Hongdu Deng, Wenhui Li, Jiali Wang, Ming Chen, Zihang Shao, Jingshu Zhang, Lanci Liu, Jie Zhang, Ping Cui, Chunyan Li, Xinyou Wang, Ying Xu, Junjun Zhang, Dan Wang, Chuansheng Wang","doi":"10.1111/adb.70166","DOIUrl":"10.1111/adb.70166","url":null,"abstract":"<p><p>Alcohol dependence (AD) is characterized by a high relapse rate. Virtual reality (VR) technology can provide immersive cue exposure therapy (VR-CET) and aversion therapy (VR-AT). This study aimed to evaluate the efficacy of VR-CET, VR-AT and their combination on craving, emotional and sleep states, attentional bias and relapse rate in patients with AD. In this single-centre randomized controlled trial, male inpatients with AD were randomly assigned to one of four groups: control, VR-CET, VR-AT or combined VR-CET + AT (target n = 25 per group; 80 completed, 20 per group). The interventions spanned 15 days with eight sessions (VR-CET + AT ~20 min/session; others ~10 min). Assessments were conducted before and after treatment using the Visual Analogue Scale (VAS), the Pennsylvania Alcohol Craving Scale (PACS), the Hamilton Depression Scale (HAMD), the Hamilton Anxiety Scale (HAMA) and the Pittsburgh Sleep Quality Index (PSQI). Eye-tracking and grasping indices in VR environments were used to assess attentional bias (e.g., alcohol-cue fixation time ratio). Relapse was evaluated by telephone at 4 and 12 weeks post-treatment. Statistical analyses used Shapiro-Wilk tests and ANOVA/Kruskal-Wallis tests with appropriate post hoc comparisons (α = 0.05). All groups showed significant pre- to post-treatment improvements in PACS, HAMD, HAMA, PSQI and VAS scores (all p < 0.001). Between-group comparisons at post-treatment revealed significant differences in alcohol-cue fixation time ratio (p < 0.05), with the VR-CET + AT group showing a lower fixation time ratio than the control group. VAS scores also differed among groups (p < 0.05), with the control group showing higher values than the VR-CET + AT group. Changes in alcohol-cue fixation time ratio from pre- to post-treatment were significantly greater in the VR-CET + AT group than in the control group. Relapse rates at 4 and 12 weeks (47/80 reached by telephone follow-up) did not significantly differ among groups (both p > 0.05). Combining VR-CET with VR-AT reduced craving (VAS) and attentional bias (alcohol-cue fixation time ratio) beyond standard care, whereas all groups improved on clinical scales. Larger and longer trials are warranted to further clarify relapse outcomes. Trial Registration: Chinese Clinical Trial Registry, ChiCTR2500110026. Registered 29 September 2025 (retrospectively registered).</p>","PeriodicalId":48966,"journal":{"name":"Addiction Biology","volume":"31 5","pages":"e70166"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844485","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":"Cortical Structure Alterations in Young People With Mild Internet Gaming Disorder.","authors":"Bohui Mei, Longyao Ma, Qiuying Tao, Jinghan Dang, Jieping Sun, Mengzhe Zhang, Jingliang Cheng, Yong Zhang","doi":"10.1111/adb.70154","DOIUrl":"10.1111/adb.70154","url":null,"abstract":"<p><p>This study aims to explore alterations in cortical structure in young individuals with early Internet gaming disorder (IGD) and to provide novel insights for early detection and intervention of disease treatment. We investigated the brain structural magnetic resonance imaging data of 64 individuals with IGD and 47 healthy controls (HCs). The grey matter volume, cortical thickness, and cortical complexity of the two groups were compared separately, and the correlations between the brain regions with structural changes and clinical characteristics in IGD patients were analyzed. Compared to HCs, the IGD group showed no significant GMV differences. However, they exhibited a distinct pattern of right-hemisphere dominant cortical thickening in regions spanning the default mode, dorsal attention, and visual networks (e.g., superior frontal gyrus [SFG], posterior cingulate and lateral occipital gyrus), concurrent with reduced cortical complexity in prefrontal and occipito-parietal areas. Our study suggests that long-term game stimulation is consistent with adaptive resource reallocation. Adolescents with mild IGD demonstrate a unique thickening-complexity decoupling pattern, where cortical thickening in game-related networks coexists with reduced complexity while GMV remains stable. This pattern could reflect a compensatory neuroadaptation phase, highlighting both a critical window for early intervention and specific neural targets for future therapeutic strategies.</p>","PeriodicalId":48966,"journal":{"name":"Addiction Biology","volume":"31 4","pages":"e70154"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13077548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677967","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":"In Vivo Imaging of Neuronal Activity Shifts in the Somatosensory Cortex After Morphine Tolerance in Mice.","authors":"Guangyan Zhang, Weiwei Meng, Ling-Jun Xu, Bin Mou, Zongqin Xiang, Xiangcai Ruan, Yong U Liu, Haihua Shu","doi":"10.1111/adb.70155","DOIUrl":"10.1111/adb.70155","url":null,"abstract":"<p><p>Morphine is widely used to treat severe pain, but its analgesic effect diminishes with repeated use due to the development of tolerance. Reversing this tolerance remains a clinical challenge, as its underlying mechanisms are complex and not fully understood. Although the involvement of multiple central nervous system regions in morphine tolerance has been established, the role of the primary somatosensory cortex (S1)-a key region for sensory perception-remains unclear. In this study, we used in vivo two-photon calcium imaging to longitudinally track neuronal activity in S1 during the induction of morphine tolerance in mice. Mice received daily morphine injections (10 mg/kg, s.c.) for 7 days. Behavioural assays confirmed the development of tolerance, as shown by diminished analgesic responses. While total neuronal activity in S1 remained stable after the first morphine injection, a significant increase was observed on Day 7. At the single-neuron level, three response patterns were identified: increased, decreased and stable firing following morphine administration. Notably, these subpopulations were dynamically restructured after tolerance was established. Our findings reveal that morphine tolerance is accompanied by network-level reorganization in the somatosensory cortex, suggesting a cortical contribution to altered sensory processing during chronic opioid exposure.</p>","PeriodicalId":48966,"journal":{"name":"Addiction Biology","volume":"31 4","pages":"e70155"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13077661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147678018","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":"Cognitive Behavioural Therapy Group Counselling for Nicotine Dependence in College Students: Behavioural and Resting-State EEG Microstate Evidence.","authors":"Jiayue Zou, Can Zhang, Xiaoyu Dai, Shaoyu Tu, Haichao Zhao, Jiali Liu, Ofir Turel, Qinghua He","doi":"10.1111/adb.70158","DOIUrl":"https://doi.org/10.1111/adb.70158","url":null,"abstract":"<p><p>Nicotine dependence is a chronic and relapsing disorder, with elevated onset risk during college years. Hence, we focus on college students and examine the immediate and short-term effects of 6-week cognitive behavioural therapy (CBT) group counselling in reducing nicotine dependence. Forty-five participants were randomly assigned to either the CBT group (n = 24) or control group (n = 21) and completed the entire 6-week intervention. Assessments included daily cigarette consumption, the Fagerström Test for Nicotine Dependence (FTND), DSM-5 Criteria for Tobacco Use Disorder (DSM-5), the Brief Questionnaire of Smoking Urges (QSU-Brief) and a 5-min eyes-closed resting-state EEG recording, administered at pre- and post-intervention. Four weeks after intervention, FTND and QSU-Brief were reassessed. Smokers in the CBT group demonstrated significant reductions in FTND, QSU-Brief, DSM-5 scores and daily cigarette consumption compared with the control group following the intervention. Moreover, QSU-Brief scores in the CBT group remained lower than those in the control group at 4-week follow-up. Furthermore, greater reductions in daily cigarette consumption were accompanied by smaller decreases in microstate class B occurrence and coverage in the CBT group. These findings suggest that CBT group counselling could be an effective intervention for nicotine dependence.</p>","PeriodicalId":48966,"journal":{"name":"Addiction Biology","volume":"31 4","pages":"e70158"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13100488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147786322","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":"AT1R in Central Nervous System Disorders: Unveiling Novel Mechanisms and Therapeutic Avenues for Addiction.","authors":"Jianan Lv, Dan Zhu, Sisi Song, Jiahui Zhou, Xiaoyu Zhang, Wenhua Zhou, Yu Liu, Zizhen Si","doi":"10.1111/adb.70152","DOIUrl":"10.1111/adb.70152","url":null,"abstract":"<p><p>Although the angiotensin II type 1 receptor (AT1R), a pivotal component of the renin-angiotensin system (RAS), is associated with cardiovascular and renal homeostasis, burgeoning evidence implicates its critical role in neuropsychiatric disorders, particularly addiction. Beyond regulating haemodynamics, AT1R activation in the central nervous system (CNS) modulates neuroinflammatory cascades, dopaminergic signalling plasticity, and stress-responsive neural circuit processes central to addiction pathophysiology. Notably, preclinical studies reveal that AT1R blockade attenuates drug-seeking behaviours by normalizing mesolimbic dopamine dysregulation and reducing glutamatergic excitotoxicity in the nucleus accumbens. This review systematically integrates contemporary evidence elucidating the dual pathophysiological roles of AT1R in CNS disorders, with particular emphasis on neurodegenerative diseases and psychiatric conditions. Crucially, we delineate two mechanistically distinct yet interconnected functions of AT1R: (1) serving as a critical mediator of maladaptive neuroplasticity during protracted exposure to addictive substances and (2) functioning as a regulator of blood-brain barrier (BBB) integrity, thereby potentiating neurotoxicant infiltration in substance use disorders. Building upon these mechanistic insights, we propose a translational framework for repurposing clinically approved AT1R antagonists as novel pharmacotherapies targeting addiction-related neurocircuitry dysregulation. By bridging molecular insights with translational opportunities, this work positions AT1R as a novel therapeutic target to address unmet clinical needs in addiction.</p>","PeriodicalId":48966,"journal":{"name":"Addiction Biology","volume":"31 4","pages":"e70152"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13077670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147678012","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":"No Relevant Associations Between Markers of Smoking Behaviour and Plasma Progesterone Concentrations: Findings From a Sex-Stratified Cohort Study.","authors":"Julia Gihl, Norman Zacharias, Sabine Hoffmann, Norbert Thürauf, Gerd Schaller, Georg Winterer, Anne Koopmann, Falk Kiefer, Johannes Kornhuber, Christiane Mühle, Bernd Lenz","doi":"10.1111/adb.70071","DOIUrl":"10.1111/adb.70071","url":null,"abstract":"<p><p>Cigarette smoking is a prevalent and critical global health issue, with inconsistent findings for its effects on endogenous progesterone concentrations. This large multicentre study investigated the associations between various markers of smoking behaviour and plasma progesterone concentrations using a sex-segregating approach. We studied 747 males aged 18-65 years and 158 peri-/postmenopausal females aged 50-65 years and assessed differences in plasma progesterone concentrations between smokers and never-smokers and associations of plasma progesterone concentrations with the Fagerström Test for Nicotine Dependence (FTND) score, cigarette pack years, age at onset of regular smoking, number of cigarettes smoked daily, exhaled carbon monoxide (CO), plasma cotinine and the Questionnaire of Smoking Urges (QSU) score. In models adjusted for age, body mass index (BMI), years of education, Alcohol Use Disorder Identification Test (AUDIT) scores, intake of any medication and study centre, and after correction for multiple hypothesis testing, there were no significant differences in plasma progesterone concentrations between smokers and never-smokers, and no significant associations between any of the mentioned markers of smoking behaviour and plasma progesterone concentrations in either males or females. The results suggest that smoking behaviour has no substantial effect on plasma progesterone concentrations and is not an important confounder in studies investigating progesterone.</p>","PeriodicalId":48966,"journal":{"name":"Addiction Biology","volume":"30 8","pages":"e70071"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144805142","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":"Ketone Supplements and Alcohol-Related Responses in Rodents.","authors":"Sarah Witley, Sebastian Blid Sköldheden, Christian E Edvardsson, Elisabet Jerlhag","doi":"10.1111/adb.70079","DOIUrl":"10.1111/adb.70079","url":null,"abstract":"<p><p>While alcohol use disorder can be treated with pharmacological interventions, ketosis is a recently proposed treatment option. Ketosis, defined by elevated concentrations of ketone bodies such as β-hydroxybutyrate (BHB), can be induced by a ketogenic diet or by supplements. As a supplement, both the salt and ester formulation of BHB rapidly increase blood ketone levels. Although preclinical studies have revealed that a ketogenic diet or a mix of ketone supplements reduces alcohol intake and alleviates withdrawal symptoms, the impact of BHB supplements on alcohol-related responses remains to be defined. We first assessed the efficacy of BHB in ester versus salt formulation on general locomotor activity, exogenous ketosis and alcohol-induced locomotor stimulation in male mice. We then investigated the impact of the BHB salt on alcohol intake in male and female rats. In attempts to define mechanisms influenced by the BHB salt, monoamines and their metabolites were measured in the nucleus accumbens (NAc), a brain region associated with alcohol reward. Initial results indicate that the BHB salt had a greater impact on ketone levels, glucose-ketone index and inhibition of alcohol-induced locomotor stimulation compared to the BHB ester, without altering the general locomotor activity. We further found that BHB salt dose-dependently lowered alcohol intake in rats of both sexes and that females responded to lower doses than males. Moreover, BHB salt elevated dopamine and noradrenaline and their metabolites in the NAc of male mice. Overall, this study provides insight into the role of BHB salt in modulating rodent alcohol-related behaviours.</p>","PeriodicalId":48966,"journal":{"name":"Addiction Biology","volume":"30 8","pages":"e70079"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12329427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795840","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}