Addiction neuroscience最新文献

{"title":"Dysfunctional network organization in opioid use disorder revealed by inhibitory control: Preliminary results from graph theoretic analyses of task-based fMRI among methadone-maintained patients","authors":"Eric A. Woodcock ,&nbsp;John Kopchick ,&nbsp;Andrew King ,&nbsp;Leslie H. Lundahl ,&nbsp;Vaibhav A. Diwadkar","doi":"10.1016/j.addicn.2025.100235","DOIUrl":"10.1016/j.addicn.2025.100235","url":null,"abstract":"<div><h3>Background</h3><div>Inhibitory control deficits are central to the pathophysiology of opioid use disorder (OUD). Relative to non-substance-using comparators, case-control studies show that OUD patients exhibit deficits in motor response inhibition proficiency and diminished functional activation in prefrontal, cingulate, and motor cortices. However, little is known about the presumably dysfunctional network interactions that underlie response inhibition deficits in OUD which motivated this study.</div></div><div><h3>Methods</h3><div>Functional magnetic resonance imaging data (TR=2.0 s, TE=35.29 ms, 2.6 mm isotropic; Siemens Verio 3T) were acquired in methadone-maintained OUD patients (n=15; 42.9±12.2yrs old; 66.7% male; 97.8±54.9mg/day methadone; 100% smokers) and well-matched non-OUD comparators (n=18; 39.5±9.0yrs old; 77.8% male; 88.9% smokers) during a motor control paradigm with conditions for response excitation (‘All-Go’) and response inhibition (‘Go/No-Go’) (four 48 s blocks of each). From each participant’s imaging data, undirected weighted graphs were generated in 246 brain nodes with 30,135 unique edges (weighted by undirected functional connectivity) to estimate each node’s Betweenness Centrality (BC) for inter-group comparison (<em>p</em>_FDR&lt;.05).</div></div><div><h3>Results</h3><div>Response proficiency did not differ between groups (<em>p</em>s&gt;0.10). During Go/No-Go, OUD patients evoked aberrantly reduced BC across 15 brain nodes (with no increases), indicative of diminished network integration across frontal, temporal, and parietal cortices, and nucleus accumbens. Higher BC in BA44 and BA9 were correlated with more attempts to discontinue opioid use among OUD patients (<em>p</em>s&lt;0.05).</div></div><div><h3>Discussion</h3><div>This is the first application of graph theoretical analyses to investigate the network connectomic bases of inhibitory control deficits in OUD. Disordered functional network integration during inhibitory control in OUD may impact patients’ ability to inhibit opioid use behavior.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"17 ","pages":"Article 100235"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-dependent hippocampal atrophy among people with methamphetamine-use experience","authors":"Hillary Schwarb ,&nbsp;Robert J. Roy ,&nbsp;Alisha L. Schaefer ,&nbsp;Robert J.R. Blair ,&nbsp;Nicholas A. Hubbard","doi":"10.1016/j.addicn.2025.100225","DOIUrl":"10.1016/j.addicn.2025.100225","url":null,"abstract":"<div><div>As methamphetamine use rates continue to climb, understanding its relationship with physical, mental, and cognitive decline is critical. While memory difficulties are common, the underlying neurobiology of these deficits are not well understood. Preclinical work suggests that, at least among male subjects, methamphetamine exposure results in volume loss in the hippocampus, a critical brain region supporting memory outcomes. Human studies investigating the effect of methamphetamine use on hippocampal volume have been equivocal. These inconsistencies may relate to sex differences and varying degrees of use and abstinence in study samples. The current study evaluated hippocampal volume and associated hippocampal-dependent memory in a sex-balanced community sample of people with recent problematic methamphetamine-use experience (<em>N</em> = 90) and methamphetamine-naïve controls (<em>N</em> = 90). While group differences in hippocampal volumes were evident for males with methamphetamine-use experience compared to the control group, no such differences were evident for females. However, hippocampal-dependent memory performance (i.e., delayed verbal recall performance) was impaired for both males and females with methamphetamine-use experience and both hippocampal volume and methamphetamine-use experience explained unique and significant variance in memory performance. These findings highlight the importance of considering sex-differences in methamphetamine addiction research.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"17 ","pages":"Article 100225"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Stress ↔ Addiction","authors":"Karl T. Schmidt ,&nbsp;Anushree Karkhanis","doi":"10.1016/j.addicn.2025.100239","DOIUrl":"10.1016/j.addicn.2025.100239","url":null,"abstract":"","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"17 ","pages":"Article 100239"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145362579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concurrent consumption of ethanol and corticosterone during adolescence alters neuroimmune sensitivity in Sprague Dawley rats","authors":"Ashley Lutzke,&nbsp;Ariana L. Velazquez,&nbsp;Sarah Trapp,&nbsp;Andrew S. Vore,&nbsp;Hannah E. Burzynski,&nbsp;Maeve E. Johnston,&nbsp;Terrence Deak","doi":"10.1016/j.addicn.2025.100218","DOIUrl":"10.1016/j.addicn.2025.100218","url":null,"abstract":"<div><div>Chronic stress and alcohol consumption influence various features of neuroimmune reactivity, including neurobehavioral outcomes, induction of neuroimmune genes, blood-brain barrier (BBB) permeability, and core body temperature regulation. The goal of the present studies was to characterize a novel model of chronic ethanol intake in which exogenous corticosterone (CORT), a principal end-product of the Hypothalamic-Pituitary-Adrenal (HPA) axis, was co-consumed in 10 % ethanol. In adolescence (P28–32), pair-housed Sprague-Dawley rats were given a single bottle containing 10 % ethanol with varying concentrations of CORT (0, 25, 50, or 100µg/mL) for 48 h, followed by 48 h of tap water. This four-day sequence was repeated for 12 cycles, ending in early adulthood (P76–80). In Experiment 1, following CORT and ethanol exposure, rats were challenged with restraint stress (30 min), and changes in neuroimmune gene expression were evaluated. Rats with a history of 10 % ethanol + 100µg/mL CORT showed increased interleukin (IL)-6 mRNA expression in the hippocampus relative to water comparators. Experiment 2 probed BBB permeability after perfusion with FITC-labeled dextran (20 kDa), and no changes were found. Remaining experiments evaluated the effects of ethanol/CORT drinking on ethanol-induced hypothermia (Experiment 3) and polyinosinic:polycytidylic acid (Poly I:C)-induced fever (Experiment 4). In females, ethanol consumption (regardless of CORT) delayed return to baseline following the hypothermic response, and in males, 25µg/mL CORT exclusively suppressed fever following Poly I:C challenge. Together, these findings validate a concurrent exposure model of intermittent CORT and ethanol which is translationally relevant to the adolescent experience, and uncovered ethanol- and CORT-induced changes in adult neuroimmune reactivity.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"16 ","pages":"Article 100218"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fos expression in the periaqueductal gray, but not the ventromedial hypothalamus, is correlated with psychosocial stress-induced cocaine-seeking behavior in rats","authors":"Nicole M. Hinds ,&nbsp;Ireneusz D. Wojtas ,&nbsp;Desta M. Pulley ,&nbsp;Stephany J. McDonald ,&nbsp;Colton D. Spencer ,&nbsp;Milena Sudarikov ,&nbsp;Nicole E. Hubbard ,&nbsp;Colin M. Kulick-Soper ,&nbsp;Samantha de Guzman ,&nbsp;Sara Hayden ,&nbsp;Jessica J. Debski ,&nbsp;Bianca Patel ,&nbsp;Douglas P. Fox ,&nbsp;Daniel F. Manvich","doi":"10.1016/j.addicn.2025.100217","DOIUrl":"10.1016/j.addicn.2025.100217","url":null,"abstract":"<div><div>Psychosocial stressors are known to promote cocaine craving and relapse in humans but are infrequently employed in preclinical relapse models. Consequently, the underlying neural circuitry by which these stressors drive cocaine seeking has not been thoroughly explored. Using Fos expression analyses, we sought to examine whether the ventromedial hypothalamus (VMH) or periaqueductal gray (PAG), two critical components of the brain’s medial hypothalamic defense system, are activated during psychosocial stress-induced cocaine seeking. Adult male and female rats self-administered cocaine (0.5 mg/kg/inf IV, fixed-ratio 1 schedule, 2 h/session) over 20 sessions. On sessions 11, 14, 17, and 20, a tactile cue was present in the operant chamber that signaled impending social defeat stress (<em>n</em> <em>=</em> 16, 8/sex), footshock stress (<em>n</em> <em>=</em> 12, 6/sex), or a no-stress control condition (<em>n</em> <em>=</em> 12, 6/sex) immediately after the session’s conclusion. Responding was subsequently extinguished, and rats were tested for reinstatement of cocaine seeking during re-exposure to the tactile cue that signaled their impending stress/no-stress post-session event. All experimental groups displayed significant reinstatement of cocaine seeking, but Fos analyses indicated that neural activity within the rostrolateral PAG (rPAGl) was selectively correlated with cocaine-seeking magnitude in the socially-defeated rats. rPAGl activation was also associated with active-defense coping behaviors during social defeat encounters and with Fos expression in prelimbic prefrontal cortex and orexin-negative cells of the lateral hypothalamus/perifornical area in males, but not females. These findings suggest a potentially novel role for the rPAGl in psychosocial stress-induced cocaine seeking.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"16 ","pages":"Article 100217"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144472380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Canabidiol prevents cocaine and caffeine sensitization modulating expression of extracellular matrix genes in the Nucleus Accumbens of male mice","authors":"José Pedro Prieto ,&nbsp;Rafael Sebastián Fort ,&nbsp;Guillermo Eastman ,&nbsp;Evangelina Coitiño ,&nbsp;Oliver Kaminski ,&nbsp;Carlos Ferreiro-Vera ,&nbsp;Verónica Sanchez de Medina ,&nbsp;María Ana Duhagon ,&nbsp;Cecilia Scorza ,&nbsp;José Roberto Sotelo-Silveira","doi":"10.1016/j.addicn.2025.100219","DOIUrl":"10.1016/j.addicn.2025.100219","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Cannabidiol (CBD), a non-psychotomimetic phytocannabinoid, has emerged as a potential therapeutic agent for psychostimulant use disorders. In recent work, we demonstrated that CBD can attenuate the expression of locomotor sensitization and enhanced metabolic activity in the nucleus accumbens (NAc) generated by the combination of cocaine and caffeine. The diverse CBD's interactions with different molecular targets makes it challenging to unravel the underlying mechanisms and pathways involved in its beneficial effects.</div></div><div><h3>Experimental approach</h3><div>In this study, we first evaluated the effect of CBD pre-treatment on a locomotor sensitization protocol with combined cocaine plus caffeine in mice. We then used high-throughput RNA-sequencing in mice’s NAc to identify the key pathways and genes involved in CBD attenuating behavioural effects.</div></div><div><h3>Key results</h3><div>CBD pre-treatment consistently reduced the locomotor sensitization induced by the combination of cocaine and caffeine. The transcriptome analysis revealed a notable enrichment of genes and functional associations related to extracellular matrix organization and cell interactions within the NAc. Additionally, neuroinflammation signalling pathways were also influenced by CBD. Specific genes, such as Tnc, emerged as noteworthy candidates for further investigation.</div></div><div><h3>Conclusion and implications</h3><div>Our study identifies pathways involved in CBD’s protective effects on cocaine and caffeine-induced sensitization. This provides valuable and novel insights into molecular mechanisms of CBD putatively associated with a protective effect on psychostimulant actions. Identified pathways and genes, particularly those related to extracellular matrix organization, offer potential therapeutic targets for future studies that may open new avenues for psychostimulant use disorder treatment strategies.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"16 ","pages":"Article 100219"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144696712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corticotrophin-releasing hormone binding protein in the basolateral amygdala: divergent roles in cocaine and opioid addiction like behaviors","authors":"Courtney P. Wood ,&nbsp;Arnav Gurha ,&nbsp;Caitlin Crook ,&nbsp;Angelica Martinez ,&nbsp;Selen Dirik ,&nbsp;Cloe Moreno ,&nbsp;Anirudh Vaiyapuri ,&nbsp;Avraham Libster ,&nbsp;Francesca Telese ,&nbsp;Giordano de Guglielmo","doi":"10.1016/j.addicn.2025.100221","DOIUrl":"10.1016/j.addicn.2025.100221","url":null,"abstract":"<div><div>Cocaine and oxycodone use disorders represent urgent public health burdens, with limited treatment options for opioid dependence and no approved pharmacotherapies for cocaine-related disorders, highlighting the critical need to uncover novel molecular targets in the addiction neurocircuitry. The basolateral amygdala (BLA) modulates withdrawal and drug-seeking behaviors in substance use disorders (SUDs), but the molecular drivers of these effects are poorly understood. Here, we investigated the role of corticotrophin-releasing hormone binding protein (CRHBP) in the BLA using viral-mediated knockdown, single-nucleus RNA sequencing (snRNA-seq), and operant self-administration in rats. snRNA-seq revealed <em>Crhbp</em> expression in BLA somatostatin-positive interneurons, with minimal presence in the central amygdala. <em>Crhbp</em> knockdown in the BLA decreased cocaine self-administration and cue-induced reinstatement, suggesting a role in sustaining stimulant addiction. Conversely, it increased oxycodone intake and progressive ratio breakpoints, indicating heightened opioid reinforcement, while also elevating cue-induced reinstatement after 24 h of abstinence, reflecting enhanced opioid-seeking. These opposing effects highlight <em>Crhbp’s</em> substance-specific influence on addiction-related behaviors in the BLA. Our findings position <em>Crhbp</em> as a potential therapeutic target gene for tailored interventions in cocaine and opioid SUDs.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"16 ","pages":"Article 100221"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144773022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial overview: monoamine signalling","authors":"","doi":"10.1016/j.addicn.2025.100223","DOIUrl":"10.1016/j.addicn.2025.100223","url":null,"abstract":"","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"16 ","pages":"Article 100223"},"PeriodicalIF":2.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144920095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The acoustic properties, syllable structure, and syllable sequences of ultrasonic vocalizations (USVs) during neonatal opioid withdrawal in FVB/N mouse substrains","authors":"Kelly K. Wingfield ,&nbsp;Teodora Misic ,&nbsp;Sophia A. Miracle ,&nbsp;Carly S. McDermott ,&nbsp;Kaahini Jain ,&nbsp;Nalia M. Abney ,&nbsp;Kayla T. Richardson ,&nbsp;Mia B. Rubman ,&nbsp;Jacob A. Beierle ,&nbsp;Elisha M. Wachman ,&nbsp;Camron D. Bryant","doi":"10.1016/j.addicn.2025.100215","DOIUrl":"10.1016/j.addicn.2025.100215","url":null,"abstract":"<div><div>Concomitant with the opioid epidemic, there has been a rise in pregnant women diagnosed with opioid use disorder and infants born with neonatal opioid withdrawal syndrome (NOWS). NOWS refers to withdrawal signs following cessation of prenatal opioid exposure that comprise neurological, gastrointestinal, and autonomic system dysfunction. A critical indicator of NOWS severity is excessive, high-pitched crying.</div><div>However, NOWS evaluation is mostly subjective, and additional cry features may not be easily recognized during clinical assessment. Thus, there is a need for more objective measures of NOWS severity. We used a third trimester-approximate opioid exposure paradigm to model NOWS traits in genetically similar inbred substrains of FVB/N mice (NJ, NCrl, NHsd, and NTac). Pups were injected twice daily from postnatal day 1 (P1) to P14 with morphine (10 mg/kg, s.c.) or saline (20 microliters/g, s.c.).</div><div>Because there were very few minor substrain differences in spontaneous withdrawalinduced ultrasonic vocalization (USV) profiles, we collapsed across substrains to evaluate the effects of morphine withdrawal on additional USV properties. We identified syllable sequences unique to morphine-withdrawn and saline-control FVB/N pups on P7 and P14. We also observed an effect of spontaneous morphine withdrawal on the acoustic properties of USVs on P7 and P14. Some withdrawal traits correlated with acoustic properties of USVs in morphine-withdrawn FVB/N pups on P7 and P14. This in-depth investigation of mouse USV features during spontaneous neonatal opioid withdrawal has implications for predicting neonatal opioid withdrawal severity in mice and applying objective approaches to understanding cries in human infants suffering from NOWS.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"16 ","pages":"Article 100215"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impacts of sex and acute stress modalities on the interoceptive stimulus properties of cocaine in rats","authors":"Karl T. Schmidt,&nbsp;Sofia M. Nelson,&nbsp;Alexis E. O’Shall,&nbsp;Ava R. Holmes,&nbsp;Sunil S. Das,&nbsp;M․Pilar Mengotti Estrada,&nbsp;Sam M. Shaffer,&nbsp;Miranda Listman,&nbsp;Holly P. Rahurahu","doi":"10.1016/j.addicn.2025.100216","DOIUrl":"10.1016/j.addicn.2025.100216","url":null,"abstract":"<div><div>Stress impacts the behavioral effects of drugs including cocaine. However, the extent of these impacts may rely on the modality of stressor. One such measure of cocaine’s effects is the drug discrimination procedure where rats are trained to respond based on interoceptive stimuli. Using this procedure, we asked whether three stress modalities (restraint, yohimbine, or wet bedding) produced effects similar to cocaine and/or altered cocaine’s discriminative stimulus properties. Previous studies suggest restraint stress substitutes for cocaine in male rats. Here we show similar results that restraint partially substitutes for cocaine depending on the training dose, in males but not females. Yohimbine under some conditions inhibits the interoceptive effects of cocaine in males but not females. Wet bedding was ineffective. Furthermore, the days to reach training criteria differed between the sexes with female rats learning to discriminate faster than male rats across two training doses. Taken together, these data highlight interactions between stressors and sex to modulate the interoceptive effects of cocaine.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"16 ","pages":"Article 100216"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}