Addiction Biology最新文献

{"title":"A Review of Exercise Interventions for Rehabilitation in Drug-Dependent Individuals","authors":"Qinghua He,&nbsp;Li Zhu,&nbsp;Zhaosong Wang,&nbsp;Hao Wang,&nbsp;Yiyi Jiang,&nbsp;Xin Wang,&nbsp;Fuxuan Luo,&nbsp;Chaoyi Zhu,&nbsp;Changlong Zhan","doi":"10.1111/adb.70098","DOIUrl":"10.1111/adb.70098","url":null,"abstract":"<p>This study systematically investigates the multidimensional rehabilitative effects and neurobiological mechanisms of exercise interventions in individuals with substance use disorders (SUDs). By synthesizing and critically analysing current evidence, the aim is to establish a theoretical framework for exercise-based rehabilitation and provide empirical support for optimizing intervention strategies. A comprehensive literature review was conducted, encompassing 39 core studies on exercise interventions in drug rehabilitation. Evidence-based medicine principles were applied to integrate mechanistic findings and evaluate effect sizes. The review focused on examining the physiological, psychological and neurobiological effects of various exercise modalities in individuals with SUD. Findings consistently demonstrate that exercise interventions are effective in reducing drug craving and withdrawal symptoms, improving overall quality of life and potentially lowering relapse rates. For individuals undergoing rehabilitation, exercise promotes improvements in physical health, psychological well-being and social functioning, while concurrently attenuating relapse vulnerability. As a nonpharmacological, multitarget intervention, exercise therapy exhibits significant potential in promoting neuroplasticity and facilitating psychological recovery in individuals with SUD. Standardized exercise prescriptions should be integrated into existing rehabilitation frameworks. Future research should emphasize comparative effectiveness across exercise modalities, explore the benefits of multimodal interventions, and further elucidate the interplay between biological, clinical and psychosocial mechanisms to enhance long-term rehabilitation outcomes.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"30 12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70098","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145716383","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":"Neutrophil Elastase (ELANE) as a Novel Neuroinflammatory Biomarker in Alcohol Use Disorder: Clinical Validation","authors":"Bo Zhang,&nbsp;JinLing Zhang,&nbsp;MengYa Zhu,&nbsp;Yong Fan,&nbsp;Yong Xue","doi":"10.1111/adb.70103","DOIUrl":"10.1111/adb.70103","url":null,"abstract":"<p>Alcohol use disorder is a severe public health problem; however, the specific mechanisms remain unclear. Our previous studies have identified ‘ELANE’ as the Hub gene in alcohol use disorder. However, its role in the clinical practice of alcohol use disorders has not been confirmed. A total of 53 healthy controls and 90 patients with alcohol use disorders were enrolled. Clinical factors were gathered, and a 1-year relapse follow-up was carried out. The group with alcohol use disorder had considerably higher ELANE concentrations than the healthy controls (<i>p</i> &lt; 0.001). Patients were categorized as high ELANE (≥ 2.7651 pg/mL, <i>n</i> = 46) or low ELANE (&lt; 2.7651 pg/mL, <i>n</i> = 44) based on the median ELANE expression level in the alcohol use disorder group. SERPINA3 was statistically significant, according to binary logistic analysis (<i>p</i> = 0.007). After 12 months of follow-up, there was no difference in event-free survival between patients with low and high ELANE levels, according to Kaplan–Meier survival analysis (<i>p</i> = 0.568). ELANE had an area under the curve of 0.8683 (<i>p</i> &lt; 0.0001), according to receiver characteristic curve analysis, and a sensitivity and specificity of 65.6% and 92.5%, respectively. According to Cox regression analysis, marital status was a negative predictor of relapse (β = −0.661; hazard ratio = 0.516; <i>p</i> = 0.038). Plasma ELANE represents a promising neuroinflammatory biomarker for AUD diagnosis, demonstrating excellent specificity albeit moderate sensitivity. The protease–antiprotease imbalance reflected by elevated ELANE and relatively decreased SERPINA3 suggests dysregulated inflammatory homeostasis in AUD. While ELANE lacks prognostic utility for relapse prediction, these findings warrant further investigation of neutrophil elastase inhibitors as potential therapeutic interventions and highlight the critical importance of social support systems in AUD recovery.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"30 12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145716349","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":"Epigenetic Landscapes of Methamphetamine Addiction: Unravelling the Diagnostic Potential of Gene Methylation","authors":"Qingxiao Hong,&nbsp;Shanshan Chen,&nbsp;Zhongze Lou,&nbsp;Weisheng Chen,&nbsp;Han Du,&nbsp;Longhui Li,&nbsp;Xiaohu Xie,&nbsp;Wenjin Xu,&nbsp;Wenhua Zhou,&nbsp;Huifen Liu","doi":"10.1111/adb.70108","DOIUrl":"10.1111/adb.70108","url":null,"abstract":"<p>Methamphetamine addiction is a chronic brain disorder involving significant neuroadaptive changes, with recent research emphasizing the role of epigenetic mechanisms, particularly DNA methylation. This study aims to evaluate the diagnostic potential of gene methylation by identifying and validating differentially methylated genes in methamphetamine-dependent individuals versus healthy controls. A genome-wide differentially methylated analysis was conducted using methylation microarray technology. Subsequently, pyrosequencing was employed for validation with an expanded sample size, examining 27 CG sites across eight candidate genes: ATP6V1C1, CES1, USP7, GABRB1, KCNQ2, LIAS, CIZ1 and GNG7. ROC curve analyses and correlation assessments with biochemical markers and drug use patterns were also performed. Significant methylation alterations were observed in GABRB1, CES1, KCNQ2 and USP7 between methamphetamine-dependent individuals and controls. Specifically, GABRB1 and KCNQ2 showed decreased methylation, while CES1 exhibited increased methylation. USP7 displayed site-specific changes. ROC curve analysis showed that a specific site in the GABRB1 gene demonstrated excellent diagnostic accuracy (AUC = 0.902). Methylation levels in CG sites in CES1 showed high diagnostic accuracy (AUC = 0.755) for methamphetamine dependence, while the AUC values for KCNQ2 and USP7 were 0.68 and 0.664, respectively, indicating moderate classification. Besides, the study revealed significant positive correlations between diastolic pressure and both the duration of methamphetamine use and KCNQ2 methylation levels. Additionally, USP7 methylation levels showed a positive correlation with the duration of drug use. These findings provide valuable insights for the development of diagnostic biomarkers and targeted therapeutic interventions. Future research will focus on elucidating the functional roles of these genes in the pathophysiology of methamphetamine addiction and their potential applications in treatment strategies.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"30 12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145716291","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":"Assessing the Effect of Abstinent Duration on Brain Function in Heroin-Dependent Individuals During Protracted Abstinence: A Resting-State fMRI Study","authors":"Xin Li,&nbsp;Wei Li,&nbsp;Jiajie Chen,&nbsp;Long Jin,&nbsp;Zhidong Wang,&nbsp;Liyang Dang,&nbsp;Wei Wang,&nbsp;Yue Qin,&nbsp;Qiang Li","doi":"10.1111/adb.70097","DOIUrl":"https://doi.org/10.1111/adb.70097","url":null,"abstract":"<p>Protracted abstinence (PA) is the commonly implemented treatment of heroin-dependent individuals (HDIs) in China. However, the effect of abstinence duration on the brain function of HDIs during PA using resting-state functional magnetic resonance imaging (fMRI) remains unclear. Fourteen HDIs who had finished PA for about 6 months (PA6), 16 HDIs who had completed PA for about 11 months (PA11) and 15 demographically matched healthy controls (HC) underwent this fMRI study. We analysed the difference in amplitude of low-frequency fluctuation (ALFF) values among the three groups. Then we analysed the difference in functional connectivity (FC) based on the differential regions of ALFF. Additionally, we examined the relationship between FC of differential brain regions and abstinence duration. The differences in ALFF among the three groups were found to be significant in the bilateral putamen and left inferior parietal lobule (single voxel <i>p</i> &lt; 0.001, cluster level <i>p</i> &lt; 0.05 and GRF-corrected). Compared with the PA6 group, the PA11 group showed lower ALFF values of the differential regions with a tendency toward the HC group. Meanwhile, the PA11 group showed lower FC between the left putamen and left insula, between the right putamen and left insula and between the left inferior parietal lobule and bilateral inferior frontal gyrus (IFG), but higher FC between the left putamen and left inferior temporal gyrus. The above FC of HDIs negatively correlated with the abstinence duration, except for the left putamen–inferior temporal gyrus FC. The prolonged abstinence duration may be useful to restore the impaired brain function of HDIs to some extent, although more data are needed to validate this in future studies.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"30 12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145686234","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":"Cocaine and Morphine Converge to Disrupt Chloride Homeostasis in Ventral Tegmental Area GABA Neurons","authors":"Anna C. Pearson,&nbsp;Blake A. Kimmey,&nbsp;Madison B. Taormina,&nbsp;William M. Holden,&nbsp;Alexey Ostroumov","doi":"10.1111/adb.70104","DOIUrl":"10.1111/adb.70104","url":null,"abstract":"<p>Identifying shared neural mechanisms influenced by diverse classes of drugs of abuse is essential for understanding addiction and for developing broad-spectrum treatments for substance use disorders. Previous studies indicate that many drugs of abuse increase dopamine output from the ventral tegmental area (VTA) by altering the balance of excitatory and inhibitory inputs onto dopamine neurons, thereby promoting maladaptive plasticity within reward circuits. Here, we demonstrate in rats that acute injections of morphine and cocaine, but not saline, disrupt chloride homeostasis in VTA GABA neurons. This disruption is characterised by a depolarised GABA_A reversal potential, impaired chloride extrusion, and posttranslational downregulation of the potassium chloride cotransporter KCC2. Although previous studies linked drug-induced posttranslational downregulation of KCC2 in the VTA to glucocorticoid receptor activation, we found that a glucocorticoid receptor antagonist did not prevent cocaine- and morphine-induced disruption of chloride homeostasis. Instead, our data show that dopamine D1/D5 receptor activation is both necessary and sufficient for these alterations. Notably, chloride homeostasis remains impaired for several weeks after volitional morphine self-administration, indicating long-lasting plasticity. These findings complement previous work on nicotine and alcohol, suggesting a shared mechanism of inhibitory plasticity in the VTA following drug exposure. Given that chloride dysregulation in VTA GABA neurons influences downstream circuit function and promotes maladaptive behaviours associated with drug use, we propose KCC2 as a promising therapeutic target for substance use disorders.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"30 12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145679200","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 Addiction Neurocircuitry and Resting-State Functional Connectivity in Cannabis Use Disorder: An fMRI Study","authors":"Hannah Thomson,&nbsp;Izelle Labuschagne,&nbsp;Arush Honnedevasthana Arun,&nbsp;Eugene McTavish,&nbsp;Hannah Sehl,&nbsp;Adam Clemente,&nbsp;Emillie Beyer,&nbsp;Marianna Quinones-Valera,&nbsp;Peter Rendell,&nbsp;Gill Terrett,&nbsp;Lisa-Marie Greenwood,&nbsp;Govinda Poudel,&nbsp;Victoria Manning,&nbsp;Chao Suo,&nbsp;Valentina Lorenzetti","doi":"10.1111/adb.70105","DOIUrl":"10.1111/adb.70105","url":null,"abstract":"<p>Cannabis use disorder (CUD) affects ~22-million people globally and is characterised by difficulties in cutting down and quitting use, but the underlying neurobiology remains unclear. We examined resting-state functional connectivity (rsFC) between regions of interest (ROIs) of the addiction neurocircuitry and the rest of the brain in 65 individuals with moderate-to-severe CUD who reported attempts to cut down or quit, compared to 42 controls, and explored the association between rsFC and cannabis exposure and related problems, to elucidate potential drivers of rsFC alterations. The CUD group showed greater rsFC than controls between ROIs implicated in reward processing and habitual substance use (i.e., nucleus accumbens, putamen and pallidum) and occipito/parietal areas implicated in salience processing and disinhibition. Putamen-occipital rsFC correlated with levels of problematic cannabis use and depression symptoms. CUD appears to show neuroadaptations of the addiction neurocircuitry, previously demonstrated in other substance use disorders.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"30 12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12675133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145670300","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":"Age-Dependent Differences in Cerebellar CB1 Receptor Expression and Its Association With Impulsivity and Alcohol Intake in Rats","authors":"Johana P. Gómez-Villatoro,&nbsp;Yalitza A. Alvarado-Ramirez,&nbsp;Octavio Amancio-Belmont,&nbsp;Mónica Méndez-Díaz","doi":"10.1111/adb.70107","DOIUrl":"10.1111/adb.70107","url":null,"abstract":"<p>The cannabinoid receptor 1 (CB1R) in the hippocampus has been involved in impulsivity and alcohol consumption in adolescent rats. However, the role of CB1R in the cerebellum, despite that structure's exceptionally high CB1R density, remains unexplored. We therefore tested the hypothesis that cerebellar CB1R contributes to regulating impulsive behaviour, alcohol consumption and seeking. Male Wistar rats, adolescent (PND25), adult (PND90) and aged (PND365), were assessed on the delay discounting task (DDT) and for voluntary alcohol intake-conditioned place preference (ACPP). CB1R levels were quantified via immunofluorescence in the CRUS II and interposed nucleus. Separate cohorts were used for voluntary alcohol consumption and alcohol-conditioned place preference (ACPP). Results showed that adolescent rats displayed significantly greater impulsivity and alcohol consumption than adults and aged rats, and only adolescents developed ACPP. CB1R expression peaked in adolescents across both cerebellar regions, but only Crus II levels correlated positively with impulsivity (<i>k</i> value), indicating a region- and age-specific contribution. These data reveal, for the first time, that CB1R in cerebellar Crus II selectively underpins adolescent impulsive choice and alcohol consumption and seeking, highlighting both a novel brain locus and a critical developmental window for endocannabinoid modulation.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"30 12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12664822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145641776","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":"Modelling Incentive Salience in Adolescent Substance Use: The Influence of Substance Cues, Alcohol Expectancies and Socio-Environmental Factors","authors":"Tommy Gunawan,&nbsp;Michael L. Thomas,&nbsp;Ty Brumback,&nbsp;Duncan B. Clark,&nbsp;David B. Goldston,&nbsp;Kate B. Nooner,&nbsp;Vijay A. Ramchandani,&nbsp;Alejandro D. Meruelo","doi":"10.1111/adb.70106","DOIUrl":"10.1111/adb.70106","url":null,"abstract":"<p>Alcohol urge regulation, drug urge regulation, motivational attitudes and alcohol expectancies have been linked to substance use, but their combined influence on reward sensitivity and behaviour remains underexplored. This is particularly critical during adolescence and young adulthood, a period of heightened susceptibility to alcohol use and risky behaviours. Using data from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA), an accelerated longitudinal design that includes all age groups at each time point, this study examined how these factors interact to shape substance use behaviours, including the onset of regular drinking, binge drinking, drug use and sexual intercourse. Exploratory and confirmatory factor analyses (EFA/CFA) utilized data from Years 7 to 9, comprising 430 participants across all age groups, to identify latent incentive-salience constructs related to urge regulation, motivational attitudes and alcohol expectancies, with a split-sample approach used to validate the factor structure in a mature cohort. Structural equation modelling (SEM) employed longitudinal data from Year 5 predictors and demographic controls to examine outcomes assessed in Year 6, leveraging the developmental focus of this age range. Covariates included age, sex and socio-economic status. EFA/CFA confirmed a robust latent structure, and SEM revealed that alcohol urge regulation significantly predicted past-year binge drinking, while drug urge regulation was negatively associated with total drug use but had no significant effect on alcohol-related behaviours. Alcohol expectancies and demographic factors, such as older age and male sex, were significantly associated with increased substance use, while socio-economic status further influenced these outcomes. Findings highlight the critical role of incentive salience in youth substance use and suggest that prevention strategies should target individual risk factors and demographic influences. Early education and supportive policies may reduce early substance use and its associated harms.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"30 12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12664821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145641692","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":"Functional Connectivity Disruptions in Grey Matter Volume-Altered Brain Regions Among Male Smokers: A Neuroimaging Study","authors":"Hui Zhang,&nbsp;Jiawen Tian,&nbsp;Xinyu Wang,&nbsp;Hongyu Zhang,&nbsp;Longyao Ma,&nbsp;Bohui Mei,&nbsp;Mengzhe Zhang,&nbsp;Qingqing Lv,&nbsp;Yarui Wei,&nbsp;Shaoqiang Han,&nbsp;Yong Zhang","doi":"10.1111/adb.70096","DOIUrl":"https://doi.org/10.1111/adb.70096","url":null,"abstract":"<p>This study aimed to investigate whether structural brain alterations in smokers are accompanied by synchronized changes in functional connectivity, with a focus on understanding the neural mechanisms underlying smoking addiction. We conducted a meta-analysis of voxel-based morphometry (VBM) studies using the Seed Mapping software package to identify consistent grey matter changes in smokers' brains, which were subsequently defined as regions of interest (ROIs). Resting-state functional connectivity between these ROIs and whole-brain voxels was analysed in 53 male smokers and 38 non-smokers. Additional correlation analyses were performed to assess relationships with clinical features. Smokers exhibited reduced functional connectivity between the right lingual gyrus (which showed increased grey matter volume) and the left calcarine sulcus. The right superior frontal gyrus (with decreased grey matter volume) suggested diminished functional connectivity with multiple regions, including the bilateral precentral and postcentral gyrus, left rolandic operculum, left inferior frontal gyrus (opercular part), left midcingulate cortex, bilateral supplementary motor area, left paracentral lobule, right inferior frontal gyrus (triangular part) and right middle frontal gyrus (GRF corrected, voxel-level <i>p</i> &lt; 0.001, cluster-level <i>p</i> &lt; 0.05). Notably, reduced connectivity of some brain regions to the right superior frontal gyrus was negatively correlated with the Fagerström Test for Nicotine Dependence (FTND). Our findings demonstrate that structural brain alterations in smokers are associated with specific disruptions in functional connectivity, particularly within visual attention, executive control and sensorimotor networks. These results provide additional evidence of the neuropathophysiological mechanisms underlying smoking addiction.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"30 12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145619149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Escalation of Ethanol Drinking in Mice Is Associated With Neurochemical Changes in the Dorsal Striatum","authors":"Eric Baetscher,&nbsp;Timothy L. Carlson,&nbsp;Connor Hilts,&nbsp;Jade L. Thomas,&nbsp;Patrick N. Reardon,&nbsp;Verginia C. Cuzon Carlson,&nbsp;Christopher D. Kroenke","doi":"10.1111/adb.70101","DOIUrl":"https://doi.org/10.1111/adb.70101","url":null,"abstract":"&lt;p&gt;Prior studies indicate that a bias towards excitation in the excitatory/inhibitory balance occurs in the dorsal striatum as a result of chronic heavy alcohol use. However, investigations of the dorsal striatum by noninvasive means, such as magnetic resonance spectroscopy (MRS) in vivo, have been lacking. In this study, 49 mice (27 female) on a C57BL/6J genetic background were subject to a chronic intermittent ethanol and forced swim stress (CIE-FSS) procedure. For each mouse, MRS data were acquired at two timepoints from a single voxel covering the dorsal striatum bilaterally. The baseline MRS timepoint occurred in an ethanol naïve state. Ethanol drinking for all mice consisted of 1-h/day access to one bottle of 15% ethanol, for 5 days/week. After a 6-week ethanol drinking acclimation period, mice were assigned to four experimental groups: air and no stress, air and stress, EtOH&lt;sub&gt;vapour&lt;/sub&gt; and no stress, and EtOH&lt;sub&gt;vapour&lt;/sub&gt; and stress. Mice then underwent four cycles of CIE-FSS, each cycle consisted of 1 week of vapour (air or ethanol) followed by 1 week of either 10 min of FSS swim stress or no swim stress, and 1-h access to 15% ethanol. A follow-up MRS timepoint occurred at the conclusion of the 14-week CIE-FSS protocol, after at least 43 h of abstinence from ethanol. Whole-cohort ethanol drinking increased from a mean ± SEM of 1.51 ± 0.11 g/kg at Week 1, to a mean of 3.15 ± 0.13 g/kg at Week 14. Robust increases in several neurochemicals were observed between baseline and follow up, with the largest increases found for glutamate, glutamine, taurine, and creatine. Two sets of analysis on MRS data were performed: (1) assessing effects of experimental group (CIE, FSS and/or sex) on striatal neurochemistry and (2) investigating correlations between longitudinal changes in ethanol drinking and changes in neurochemical concentrations. Striatal neurochemical concentrations exhibited CIE-FSS group effects (1), notably EtOH&lt;sub&gt;vapour&lt;/sub&gt; exposure significantly reduced lactate concentrations at follow up. The change in glutamate between baseline and follow up was significantly lower in EtOH&lt;sub&gt;vapour&lt;/sub&gt; exposed mice. Changes in the glutamate/glutamine ratio were markedly reduced in the EtOH&lt;sub&gt;vapour&lt;/sub&gt; condition. In our correlational analysis (2) of changes in drinking versus changes in neurochemical concentrations from baseline to follow up, we found that female mice have strong positive linear correlations between the change in ethanol drinking and the changes in concentration of glutamate, glutamine, taurine, myo-inositol and creatine. In male mice, inverse correlations were found between changes in drinking and changes in glutamate, taurine and creatine concentrations. Additionally, the change in cerebral ventricle volume was found to correlate with the change in ethanol drinking, but ventricular volume change was not significantly affected by CIE or FSS. Together, the observed effects of CIE on MRS outcomes in dorsal stri","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"30 12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/adb.70101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145595382","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}