Addiction Biology最新文献

{"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>_{<i>generic</i>} = 8.83E-03 vs. <i>p</i>_{<i>exposed</i>} = 1.83E-02) and genetic correlations with prior OUD GWAS (<i>r</i>_{<i>g-generic</i>} = 0.83 ± 0.26 vs. <i>r</i>_{<i>g-exposed</i>} = 0.78 ± 0.27). Although GWASs were limited by sample size (<i>N</i>_generic = 6269, <i>N</i>_exposed = 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}

{"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}

{"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}

{"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}

{"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}

{"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}

{"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}

{"title":"Behavioural, Neural and Molecular Effects Underlying Caffeine's Addictive Properties","authors":"Xiaonan Li,&nbsp;Fei Fei,&nbsp;Xiaomin Liu,&nbsp;Peicai Cui,&nbsp;Huaquan Sheng,&nbsp;Ying He,&nbsp;Yi Shen,&nbsp;Yihan Gao","doi":"10.1111/adb.70114","DOIUrl":"10.1111/adb.70114","url":null,"abstract":"<p>Caffeine is one of the most widely consumed psychoactive substances globally. It acts as a non-selective adenosine receptor antagonist. Despite its extensive use, the effects of caffeine on the central nervous system remain poorly understood. This study aims to investigate the behavioural changes and underlying neural mechanisms associated with caffeine addiction. The results of conditioned place preference (CPP) revealed that caffeine induces a strong preference shift, demonstrating its rewarding properties. 3D Behavioural Profiling and Motion Analysis further demonstrated significant differences in locomotion, rearing and sniffing behaviours between caffeine-treated and saline-treated groups. C-fos and fibre photometry experiments revealed that caffeine activates the medial prefrontal cortex (mPFC) region. Transcriptomic profiling revealed a significant enrichment of pathways associated with transcriptional regulation and calcium signalling in the medial prefrontal cortex (mPFC) of caffeine-treated mice. Together, these findings provide a multidimensional perspective on caffeine's addictive properties, as well as its modulation of mPFC activity and molecular pathways. This contributes to a deeper understanding of caffeine's effects on the central nervous system.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"30 12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12718699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145806338","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":"Methcathinone Neurotoxicity in the Rat Prefrontal Cortex by Integrated Synaptic Changes and Transcriptome Analysis","authors":"Rukui Zhou,&nbsp;Yingwen Xu,&nbsp;Chunming Xu,&nbsp;zhe Chen,&nbsp;Jieping Lv,&nbsp;Keming Yun,&nbsp;Zhiwen Wei","doi":"10.1111/adb.70113","DOIUrl":"10.1111/adb.70113","url":null,"abstract":"<p>Long-term abuse of methcathinone reduces grey matter volume in the prefrontal cortex and consequently impairs learning and memory abilities. However, the exact mechanism of damage remains unknown. Therefore, this study aimed to analyse the potential mechanisms underlying methcathinone-induced neural damage using transcriptomic analysis. Accordingly, 32 Sprague Dawley rats were randomly divided into four groups: control, low-dose, medium-dose and high-dose. Low, medium and high methcathinone doses (0.25, 5 and 20 mg/kg) were administered to the animals in the three treatment groups once daily via intraperitoneal injection for 2 weeks. Finally, the learning and memory functions of all the animals were tested using the Morris water maze. Electron microscopy and Golgi staining were used to observe changes in synaptic structure, and transcriptome sequencing was performed in the prefrontal cortex of the control and high-dose groups. Key differentially expressed genes were quantified using quantitative real-time reverse transcription polymerase chain reaction. Collectively, methcathinone induced learning and memory decline in rats and destroyed the synaptic structure of the rat prefrontal cortex. In the transcriptomic analysis, 1457 (694 up-regulated and 763 down-regulated) genes were differentially expressed in the prefrontal cortex of rats in the high-concentration group compared to that in the control group. Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes analysis revealed that differential genes were enriched in synapses, neurotransmitter systems, homeostasis of Ca²⁺ concentration and membrane potential regulation. This indicates that methcathinone adversely affects neurotransmitter regulation, Ca²⁺ signalling and membrane potential regulation, thereby destroying synapse structure and causing learning and memory dysfunction. Combined with the above molecular mechanisms, seven key genes were identified: nerve growth factor (NGF), dopamine receptor D1 (DRD1), dopamine receptor D2 (DRD2), solute carrier family 1 member 2 (SLC1A2), calcium/calmodulin-dependent protein kinase II alpha (CAMK2A), synaptotagmin 1 (SYT1) and glutamate ionotropic receptor <i>N</i>-methyl-<span>d</span>-aspartate type subunit 2A (GRIN2A). This study demonstrates that methcathinone causes neural damage and provides possible molecular mechanisms and target genes to clarify the mechanism of methcathinone-induced neural damage.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"30 12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12715272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783386","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":"Behavioural and Neural Reliability of a Pavlovian-to-Instrumental Transfer Task","authors":"Matthew J. Belanger,&nbsp;Hao Chen,&nbsp;Juliane H. Fröhner,&nbsp;Maria Garbusow,&nbsp;Andreas Heinz,&nbsp;Michael N. Smolka","doi":"10.1111/adb.70112","DOIUrl":"10.1111/adb.70112","url":null,"abstract":"<p>The use of Pavlovian-to-instrumental transfer (PIT) in addiction research is on the rise as a means of assessing an individual's susceptibility to interference between Pavlovian and instrumental control over behaviour. However, the reliability of PIT tasks has been rarely assessed.The present study provides an investigation of the reliability of PIT, both on a behavioural and neural level, examining split-half as well as test–retest reliability. We assessed two different samples: (1) a mixed detoxified alcohol-dependent sample (with controls) comprising 119 behavioural and 69 fMRI datasets assessed twice within 3–4 weeks and (2) a developmental sample with 117 behavioural and 91 fMRI datasets assessed twice after 3 years. We computed two behavioural parameters of PIT (interference and motivational PIT effects) that were used in our previous studies. The interference PIT effect was assessed as the difference in error rates between the congruent and incongruent trials of the PIT task. The motivational PIT effect was assessed as the linear relationship between the number of button presses influenced by Pavlovian-conditioned environmental cues. We further assessed the reliability of four predefined fMRI PIT contrasts.On the behavioural level, our results revealed excellent split-half reliability for both the interference (<i>r</i> = 0.92–0.97) and motivational (<i>r</i> = 0.94–0.98) aspects of PIT in both clinical and developmental samples. In comparison, test–retest reliability after 3 weeks was lower (clinical sample: ICC = 0.53) and again lower yet still significant despite neurodevelopmental brain maturation after 3 years (developmental sample: ICC = 0.26–0.29). In the fMRI analysis, regions of interest showed acceptable ICCs in the incongruent and congruent contrasts (split-half: 0.59–0.80; test–retest: 0.13–0.51). Global overlap assessments using Jaccard coefficients revealed individual-level variability in neural responses (split-half: 47%–51% overlap; test–retest: 29%–35% depending on the sample and contrast). All fMRI reliability coefficients for the motivational PIT effect were below 0.17.Overall, behavioural PIT reliability was good, especially from the split-half perspective. For neuroimaging, the incongruent contrast seems best suited for predicting individual outcomes, while the neural motivational PIT effect seems to represent more changeable current states.</p>","PeriodicalId":7289,"journal":{"name":"Addiction Biology","volume":"30 12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12714411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783399","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}