Addiction neuroscience最新文献

{"title":"Endogenous regulator of G protein signaling 14 (RGS14) blunts cocaine-induced emotionally motivated behaviors in female mice","authors":"Sara N. Bramlett ,&nbsp;Stephanie L. Foster ,&nbsp;David Weinshenker ,&nbsp;John R. Hepler","doi":"10.1016/j.addicn.2025.100203","DOIUrl":"10.1016/j.addicn.2025.100203","url":null,"abstract":"<div><div>Addictive drugs hijack the neuronal mechanisms of learning and memory in motivation and emotion processing circuits to reinforce their own use. Regulator of G-protein Signaling 14 (RGS14) is a natural suppressor of post-synaptic plasticity underlying learning and memory in the hippocampus. The present study used immunofluorescence and RGS14 knockout mice to assess the role of RGS14 in behavioral plasticity and reward learning induced by chronic cocaine in emotional-motivational pathways. We report that RGS14 is strongly expressed in discrete regions of the ventral striatum and extended amygdala in wild-type mice, and is co-expressed with D1 and D2 dopamine receptors in neurons of the nucleus accumbens. Of note, we found that RGS14 is upregulated in the nucleus accumbens following acute cocaine treatment in mice with chronic cocaine history. We found significantly increased cocaine-induced locomotor sensitization, as well as enhanced conditioned place preference and conditioned locomotor activity in RGS14-deficient mice compared to wild-type littermates. Together, these findings suggest that endogenous RGS14 suppresses cocaine-induced plasticity in emotional-motivational pathways, implicating RGS14 as a protective agent against the maladaptive neuroplastic changes that occur during addiction.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"15 ","pages":"Article 100203"},"PeriodicalIF":0.0,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Presence of distinct operant phenotypes and transient withdrawal-induced escalation of operant ethanol intake in female rats","authors":"Joseph R Pitock,&nbsp;Shannon R Wheeler,&nbsp;Arleen Perez Ayala,&nbsp;Shikun Hou,&nbsp;Nathaly M Arce Soto,&nbsp;Elizabeth J Glover","doi":"10.1016/j.addicn.2025.100198","DOIUrl":"10.1016/j.addicn.2025.100198","url":null,"abstract":"<div><div>Operant self-administration is frequently used to investigate the neurobiological mechanisms underlying alcohol seeking and drinking and to evaluate treatments of alcohol use disorder (AUD). Although widely used by the research community, there is a paucity of operant ethanol self-administration studies that include female subjects. The current study characterizes home cage drinking and operant ethanol self-administration in female Sprague Dawley, Long Evans, and Wistar rats. Rats underwent three weeks of intermittent-access two-bottle choice home cage drinking before being trained to lever press for ethanol in standard operant chambers equipped with contact lickometers. After capturing baseline operant performance, rats were chronically exposed to control or ethanol liquid diet using the Lieber-DeCarli method followed by re-evaluation of operant performance during acute withdrawal. Our findings reveal the presence of three distinct operant phenotypes, the prevalence of which within each strain is strikingly similar to our previous observations in males. Within a given phenotype, rats of each strain performed similarly during operant testing. Ethanol intake during home cage drinking was unable to predict future operant phenotype. Relative to controls, Drinkers chronically exposed to ethanol liquid diet exhibited a significant, but transient, escalation in consummatory, but not appetitive, responding during acute withdrawal. Collectively, these data closely parallel many of our previous observations in males while also highlighting potential sex differences in drinking strategies following dependence. Our findings provide new insight into similarities and differences in operant ethanol self-administration between males and females and emphasize the importance of including females in future studies of ethanol drinking and dependence.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"15 ","pages":"Article 100198"},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143303053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biotin's protective effects against nicotine withdrawal-induced anxiety and depression: Mechanistic insights into serotonin, inflammation, BDNF, and oxidative stress in male rats","authors":"Dawood Hossaini ,&nbsp;Mohammad Jalal Nazari ,&nbsp;Khan Baba Ghazanfar ,&nbsp;Mohammad Edris Amiri ,&nbsp;Mohammad Tariq Anwary ,&nbsp;Mohammad Jawad Jawad ,&nbsp;Murtaza Haidary","doi":"10.1016/j.addicn.2025.100199","DOIUrl":"10.1016/j.addicn.2025.100199","url":null,"abstract":"<div><h3>Introduction</h3><div>Substance use disorders, particularly nicotine use disorders, represent a significant public health problem, with adolescents particularly vulnerable to their adverse effects. This study examined the potential anxiolytic and antidepressant effects of biotin in attenuating the behavioral and neurobiological changes associated with nicotine withdrawal in adolescent rats.</div></div><div><h3>Materials and Methods</h3><div>Sixty male Sprague-Dawley rats were subjected to nicotine administration and subsequently, nicotine withdrawal, after which behavioral assessments included the open-field test, the elevated plus-maze test, and the forced-swimming test performed after withdrawal to assess anxiety and depression behaviors. We also performed biochemical analyses to measure serotonin levels, monoamine oxidase A activity, brain neurotrophic factor concentration, and markers of oxidative stress.</div></div><div><h3>Results</h3><div>The results demonstrated that nicotine withdrawal intensifies behavioral symptoms of anxiety and depression by disrupting serotonin metabolism, triggering inflammatory responses, and upsetting the balance of oxidative stress. Treatment with biotin, particularly at higher doses, significantly alleviated these withdrawal-induced behavioral changes. Mechanistically, biotin was found to increase serotonin levels and decrease monoamine oxidase Activity, elevate brain-derived neurotrophic factor levels, reduce glial fibrillary acidic protein expression, and improve oxidative stress balance within the cortical tissue.</div></div><div><h3>Discussion</h3><div>This study suggests that biotin may have significant therapeutic potential for alleviating the side effects associated with nicotine withdrawal, particularly anxiety and depression. Given the complex neurobiological mechanisms underlying withdrawal symptoms, biotin's ability to modulate critical signaling pathways such as serotonin metabolism, neuroinflammation, and oxidative stress could provide a multifaceted treatment approach.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"15 ","pages":"Article 100199"},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143153816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the impact of concurrent sucrose availability on operant ethanol self-administration in male and female Long Evans rats","authors":"Olivia A. Ortelli,&nbsp;Jeffrey L. Weiner","doi":"10.1016/j.addicn.2025.100196","DOIUrl":"10.1016/j.addicn.2025.100196","url":null,"abstract":"<div><div>Investigating how environmental factors, such as the availability of non-ethanol alternative reinforcers, influences ethanol self-administration is critical for understanding the pathology of alcohol use disorder (AUD). Here we established the first operant choice paradigm that leverages the strengths of the sipper tube self-administration model to investigate how concurrent access to sucrose altered ethanol self-administration in male and female Long Evans rats. Choice behavior was examined using two distinct paradigms, including a novel adaptation of the response requirement paradigm. Under both a fixed-ratio or response requirement paradigm, we observed that concurrent availability of an alternative reinforcer significantly reduced appetitive and consummatory ethanol drinking-related behaviors. Furthermore, we assessed the sensitivity of the response requirement choice paradigm by administering the pharmacological stressor yohimbine and by altering the taste of the ethanol solution. Yohimbine administration non-selectively increased ethanol and sucrose intake, but not seeking, while taste adulteration decreased ethanol seeking and intake. These experiments demonstrate the utility of two concurrent choice paradigms that can more accurately capture AUD-like phenotypes, such as ethanol-directed choice in the face of alternative reinforcers. Future studies should investigate how models of vulnerability and dependence alter ethanol choice behavior under these paradigms.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"14 ","pages":"Article 100196"},"PeriodicalIF":0.0,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143169127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxytocin attenuates demand for cocaine in female rats","authors":"Amy S. Kohtz ,&nbsp;Hannah Davies ,&nbsp;Belle Lin ,&nbsp;Gary Aston-Jones","doi":"10.1016/j.addicn.2025.100197","DOIUrl":"10.1016/j.addicn.2025.100197","url":null,"abstract":"<div><div>There are substantial sex differences in substance use disorders (SUDs), and a key feature of SUD is pathologically high economic demand for drug. The hypothalamic neuropeptide oxytocin (OXT) is heavily implicated in the modern treatment of SUDs. Using a within-session threshold behavioral economics (BE) procedure, we quantified demand elasticity (a, inverse motivation) and free consumption (Q₀) in male and female rats to investigate the effect of OXT on cocaine demand. Results showed that OXT decreased motivation for cocaine; an effect greater during the high-demand phase (diestrus, low progesterone, P₄) vs low demand phases (proestrus, high P₄). We confirmed our prior findings that P₄ attenuates cocaine demand in female rats and that chronic cocaine self-administration disrupts estrus cyclicity. Following each injection, OXT at either 0.1mg/kg or 0.3mg/kg restored estrous cycling in intact females with prior cocaine experience for one week and remained effective with up to 4 weeks of injections. Fos reactivity in OXT+ neurons was greater when rats were in proestrus compared to diestrus and significantly correlated to motivation and circulating levels of P₄. Finally, using ovariectomized females with P₄ replacement, we show that P₄’s demand attenuating effects are reversed by atosiban (1.0 mg/kg, IP), an OXT antagonist. These data show an interaction between oxytocin and progesterone in female rats that may underlie differences in cocaine demand between sexes. Additionally, we show critical periods for using OXT as a treatment to reduce cocaine demand in females. Our results indicate novel therapeutic treatments for SUDs must be tailored to hormonal states.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"15 ","pages":"Article 100197"},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143153818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concurrent and prospective relations between aberrant stress-induced frontal alpha asymmetry and cannabis use disorder","authors":"Brandon S. Schermitzler ,&nbsp;Julia Y. Gorday ,&nbsp;Michael Griffin ,&nbsp;Richard J. Macatee","doi":"10.1016/j.addicn.2025.100195","DOIUrl":"10.1016/j.addicn.2025.100195","url":null,"abstract":"<div><h3>Background</h3><div>Cannabis Use Disorder (CUD) is prevalent and associated with significant disability. Stress potentiation of drug use motivation is a mechanism implicated in CUD; however, little is known about the neurobiological mechanisms through which stress impacts cannabis use motivation. Frontal alpha asymmetry (FAA), an index of approach motivation, is sensitive to acute stress, so this study sought to examine the relationship between stress-potentiated FAA and cannabis-related problems.</div></div><div><h3>Method</h3><div>Non-treatment-seeking regular cannabis users in a stress task study (<em>N</em> = 102) and a control task study (<em>N</em> = 52) completed a resting state task with concurrent electroencephalogram recording before and after a stressor or control task. Changes in FAA from pre- to post-task represented a neurophysiological index of approach motivation change. Participants completed self-report and clinician-assessed measures of cannabis-related problems. Participants in the stress study re-completed all study components three months later.</div></div><div><h3>Results</h3><div>Relative to the control study, participants in the stress study showed a greater shift from right to left alpha-band power at frontal sites. More cannabis-related problems, but not past-month cannabis use sessions, correlated with a blunted stress-induced FAA response, which predicted greater maintenance of cannabis-related problems three months later. Baseline cannabis-related problems were not associated with changes in the stress-induced FAA response from baseline to follow-up, and changes in cannabis-related problems across the three-month study period were not associated with changes in the stress-induced FAA response. The stress-induced FAA response demonstrated good stability over three months.</div></div><div><h3>Conclusion</h3><div>The stress-induced FAA response may represent a stable predictor of cannabis-related problems and may have implications for clinical practice.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"14 ","pages":"Article 100195"},"PeriodicalIF":0.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143169129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Central amygdala neuroimmune signaling in alcohol use disorder","authors":"Mariam Melkumyan ,&nbsp;Patrick A. Randall ,&nbsp;Yuval Silberman","doi":"10.1016/j.addicn.2024.100194","DOIUrl":"10.1016/j.addicn.2024.100194","url":null,"abstract":"<div><div>Alcohol Use Disorder (AUD) is a prevalent and debilitating condition characterized by an inability to control alcohol consumption despite adverse consequences. Current treatments for AUD, including FDA-approved medications such as naltrexone and acamprosate, have limited efficacy and compliance, underscoring the need for novel therapeutic approaches. The central amygdala (CeA) plays a crucial role in the development and maintenance of AUD, particularly aspects associated with stress and binge behaviors. Recent research indicates neuroimmune signaling in the CeA is emerging as a key factor in this process. Chronic alcohol consumption disrupts neuroimmune signaling, leading to altered cytokine expression and activation of glial cells, including astrocytes and microglia. These changes contribute to the dysregulation of neural circuits involved in reward and stress, perpetuating alcohol-seeking behavior and relapse. This review delves into how chronic alcohol exposure affects neuroimmune signaling in the CeA, contributing to the pathophysiology of AUD. By focusing on the impact of cytokine expression and glial cell activation, this review aims to elucidate the mechanisms by which neuroinflammation in the CeA influences alcohol-related behaviors. By providing a comprehensive overview of the current state of research, this review identifies potential therapeutic targets for AUD. Understanding the complex interplay between neuroimmune signaling and alcohol-related behaviors may pave the way for more effective treatments and improved outcomes for individuals struggling with AUD.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"14 ","pages":"Article 100194"},"PeriodicalIF":0.0,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143169125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuronal heterogeneity in the ventral tegmental area: Distinct contributions to reward circuitry and motivated behavior","authors":"N. Dalton Fitzgerald,&nbsp;Jeremy J. Day","doi":"10.1016/j.addicn.2024.100191","DOIUrl":"10.1016/j.addicn.2024.100191","url":null,"abstract":"<div><div>The ventral tegmental area (VTA) is a critical component of brain reward circuitry that influences motivation, learning, and emotional regulation. Although this role was traditionally attributed primarily to VTA dopamine (DA) neurons, recent advances in transcriptomics and intersectional genetics have revealed significant cell type heterogeneity within the VTA, challenging these established notions. Distinct subtypes of DA neurons can be identified across the VTA and substantia nigra pars compacta (SNc) by characteristics that include gene expression patterns (molecular identity), connectivity motifs (network identity), and patterns of task-linked activity and neurotransmitter release (computational identity). This review aims to synthesize current knowledge of diverse neuronal populations in the VTA, including distinct subtypes of DA, glutamate (GLUT), and GABAergic neurons and combinatorial cells alongside well-characterized markers of these neuronal subclasses. Furthermore, this review highlights known projection targets and the role of diverse VTA cell types in motivated behavior. Finally, we highlight emerging intersectional techniques that enable targeted studies of the vast array of cell types and discuss areas of research important for the future direction of the field. Understanding VTA cell type heterogeneity may yield new insights into the reward system, offering potential avenues for treating substance use disorders and other related conditions.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"14 ","pages":"Article 100191"},"PeriodicalIF":0.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143169128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential roles for vitamin D in preventing and treating impulse control disorders, behavioral addictions, and substance use disorders: A scoping review","authors":"Laya Jalilian-Khave ,&nbsp;Razi Kitaneh ,&nbsp;Binah Baht Ysrayl ,&nbsp;Anna Borelli ,&nbsp;Melissa C. Funaro ,&nbsp;Marc N. Potenza ,&nbsp;Gustavo A. Angarita","doi":"10.1016/j.addicn.2024.100190","DOIUrl":"10.1016/j.addicn.2024.100190","url":null,"abstract":"<div><div>Vitamin D deficiency is a problem of endemic proportions. Vitamin D is a major regulator of dopaminergic and serotonergic circuits, pathways implicated in addictive disorders. This scoping review (OSF registered as 67yhb) examines preclinical and clinical studies exploring relationships between vitamin D in impulse control disorders, behavioral addictions, and substance use disorders. We searched Ovid MEDLINE, Embase, APA PsycInfo, Cochrane Library, Web of Science, and Scopus databases. We extracted and summarized quantitative and qualitative data through a narrative synthesis and assessed the quality of studies using the Joanna Briggs Institute (JBI) and SYRCLE (Systematic Review Centre for Laboratory Animal Experimentation) criteria. Of 5,442 initial records identified, 28 preclinical and clinical studies were included. For most conditions, we found a negative relationship between vitamin D levels and symptom presence and/or severity. While data suggest a potential beneficial effect of vitamin D on preventing or treating these conditions, there were significant limitations identified by the JBI and SYRCLE assessments. Future studies should include impulse control disorders and other under-explored conditions, address heterogeneity regarding forms, doses, and duration of exposures to vitamin D, and explore vitamin D's potential therapeutic mechanisms.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"14 ","pages":"Article 100190"},"PeriodicalIF":0.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serotonin circuits act cooperatively with pathophysiology of opioid use disorder","authors":"Arakawa Hiroyuki ,&nbsp;Ozawa Akihiko","doi":"10.1016/j.addicn.2024.100187","DOIUrl":"10.1016/j.addicn.2024.100187","url":null,"abstract":"<div><div>Opioid abuse and its negative effect have become a critical epidemic, putting our health and society in jeopardy. Opioids are effective treatment for pain, but at risk for developing associated health threatening impacts including the euphoria associated relapsing effects, persistent occurrence with addictive and withdrawal symptoms, and consequent respiratory depression and apnea. The opioid use disorder (OUD), represented as those recurring phases of symptoms, is initiated with mediation of opioid receptor signaling pathway and subsequent neurocircuitry transformation with homeostatic and motivational change. It has been imperative to establish modulatory mechanisms and alternative treatments to mitigate OUD. This review deals with central serotonin (5-HT) system as a cooperative mediator with OUD-related neural processing. We briefly introduce molecular base of opioid receptors and available research tools in mouse models and examine OUD-phase dependent circuit mechanisms, including pain, addiction, and respiratory depression. We interrogate the potential neural roles of 5-HT in OUD-related symptoms including 5-HT toxicity and pathophysiology and discuss potential availability of 5-HT-related agents as a neuromodulatory therapeutic interacting with opioid mediated neural mechanisms and the OUD-related symptoms.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"14 ","pages":"Article 100187"},"PeriodicalIF":0.0,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}