Pub Date : 2025-01-18DOI: 10.1016/j.addicn.2025.100196
Olivia A. Ortelli, Jeffrey L. Weiner
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.
{"title":"Evaluating the impact of concurrent sucrose availability on operant ethanol self-administration in male and female Long Evans rats","authors":"Olivia A. Ortelli, 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}
Pub Date : 2025-01-15DOI: 10.1016/j.addicn.2025.100197
Amy S. Kohtz , Hannah Davies , Belle Lin , Gary Aston-Jones
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.
{"title":"Oxytocin attenuates demand for cocaine in female rats","authors":"Amy S. Kohtz , Hannah Davies , Belle Lin , 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 (Q<sub>0</sub>) 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, P<sub>4</sub>) vs low demand phases (proestrus, high P<sub>4</sub>). We confirmed our prior findings that P<sub>4</sub> 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 P<sub>4</sub>. Finally, using ovariectomized females with P<sub>4</sub> replacement, we show that P<sub>4</sub>’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}
Pub Date : 2025-01-09DOI: 10.1016/j.addicn.2025.100195
Brandon S. Schermitzler , Julia Y. Gorday , Michael Griffin , Richard J. Macatee
Background
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.
Method
Non-treatment-seeking regular cannabis users in a stress task study (N = 102) and a control task study (N = 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.
Results
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.
Conclusion
The stress-induced FAA response may represent a stable predictor of cannabis-related problems and may have implications for clinical practice.
{"title":"Concurrent and prospective relations between aberrant stress-induced frontal alpha asymmetry and cannabis use disorder","authors":"Brandon S. Schermitzler , Julia Y. Gorday , Michael Griffin , 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}
Pub Date : 2024-12-21DOI: 10.1016/j.addicn.2024.100194
Mariam Melkumyan , Patrick A. Randall , Yuval Silberman
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.
{"title":"Central amygdala neuroimmune signaling in alcohol use disorder","authors":"Mariam Melkumyan , Patrick A. Randall , 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}
Pub Date : 2024-12-13DOI: 10.1016/j.addicn.2024.100193
William S. Conrad , Lucie Oriol , Grace J. Kollman , Lauren Faget , Thomas S. Hnasko
{"title":"Corrigendum to “Proportion and distribution of neurotransmitter-defined cell types in the ventral tegmental area and substantia nigra pars compacta” [Addiction Neuroscience 13 (2024) 100183]","authors":"William S. Conrad , Lucie Oriol , Grace J. Kollman , Lauren Faget , Thomas S. Hnasko","doi":"10.1016/j.addicn.2024.100193","DOIUrl":"10.1016/j.addicn.2024.100193","url":null,"abstract":"","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"15 ","pages":"Article 100193"},"PeriodicalIF":0.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562929","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}
Pub Date : 2024-11-28DOI: 10.1016/j.addicn.2024.100191
N. Dalton Fitzgerald, Jeremy J. Day
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.
{"title":"Neuronal heterogeneity in the ventral tegmental area: Distinct contributions to reward circuitry and motivated behavior","authors":"N. Dalton Fitzgerald, 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}
Pub Date : 2024-11-26DOI: 10.1016/j.addicn.2024.100190
Laya Jalilian-Khave , Razi Kitaneh , Binah Baht Ysrayl , Anna Borelli , Melissa C. Funaro , Marc N. Potenza , Gustavo A. Angarita
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.
维生素D缺乏是一个地方性的问题。维生素D是多巴胺能和血清素能回路的主要调节剂,与成瘾性疾病有关。本综述(OSF注册号为67yhb)检查了临床前和临床研究,探讨了维生素D在冲动控制障碍、行为成瘾和物质使用障碍中的关系。我们检索了Ovid MEDLINE、Embase、APA PsycInfo、Cochrane Library、Web of Science和Scopus数据库。我们通过叙述性综合提取和总结定量和定性数据,并使用乔安娜布里格斯研究所(JBI)和sycle(实验动物实验系统审查中心)标准评估研究质量。在确定的5442份初始记录中,包括28份临床前和临床研究。在大多数情况下,我们发现维生素D水平与症状存在和/或严重程度呈负相关。虽然数据表明维生素D对预防或治疗这些疾病有潜在的有益作用,但JBI和sycle评估发现了显著的局限性。未来的研究应该包括冲动控制障碍和其他未被探索的条件,解决维生素D的形式、剂量和暴露时间的异质性,并探索维生素D的潜在治疗机制。
{"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 , Razi Kitaneh , Binah Baht Ysrayl , Anna Borelli , Melissa C. Funaro , Marc N. Potenza , 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}
Pub Date : 2024-11-24DOI: 10.1016/j.addicn.2024.100187
Arakawa Hiroyuki , Ozawa Akihiko
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.
{"title":"Serotonin circuits act cooperatively with pathophysiology of opioid use disorder","authors":"Arakawa Hiroyuki , 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}
Pub Date : 2024-11-09DOI: 10.1016/j.addicn.2024.100186
Jocelyn M. Richard , Bailey Newell , Preethi Muruganandan , Patricia H. Janak , Benjamin T. Saunders
Cues paired with alcohol can be potent drivers of craving, alcohol-seeking, consumption, and relapse. While the ventral pallidum is implicated in appetitive and consummatory responses across several reward classes and types of behaviors, its role in behavioral responses to Pavlovian alcohol cues has not previously been established. Here, we tested the impact of optogenetic inhibition of ventral pallidum on Pavlovian-conditioned alcohol-seeking in male Long Evans rats. Rats underwent Pavlovian conditioning with an auditory cue predicting alcohol delivery to a reward port and a control cue predicting no alcohol delivery, until they consistently entered the reward port more during the alcohol cue than the control cue. We then tested the within-session effects of optogenetic inhibition during 50 % of cue presentations. We found that optogenetic inhibition of ventral pallidum during the alcohol cue reduced port entry likelihood and time spent in the port, and increased port entry latency. Overall, these results suggest that normal ventral pallidum activity is necessary for Pavlovian alcohol-seeking.
{"title":"Pavlovian cue-evoked alcohol seeking is disrupted by ventral pallidal inhibition","authors":"Jocelyn M. Richard , Bailey Newell , Preethi Muruganandan , Patricia H. Janak , Benjamin T. Saunders","doi":"10.1016/j.addicn.2024.100186","DOIUrl":"10.1016/j.addicn.2024.100186","url":null,"abstract":"<div><div>Cues paired with alcohol can be potent drivers of craving, alcohol-seeking, consumption, and relapse. While the ventral pallidum is implicated in appetitive and consummatory responses across several reward classes and types of behaviors, its role in behavioral responses to Pavlovian alcohol cues has not previously been established. Here, we tested the impact of optogenetic inhibition of ventral pallidum on Pavlovian-conditioned alcohol-seeking in male Long Evans rats. Rats underwent Pavlovian conditioning with an auditory cue predicting alcohol delivery to a reward port and a control cue predicting no alcohol delivery, until they consistently entered the reward port more during the alcohol cue than the control cue. We then tested the within-session effects of optogenetic inhibition during 50 % of cue presentations. We found that optogenetic inhibition of ventral pallidum during the alcohol cue reduced port entry likelihood and time spent in the port, and increased port entry latency. Overall, these results suggest that normal ventral pallidum activity is necessary for Pavlovian alcohol-seeking.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"13 ","pages":"Article 100186"},"PeriodicalIF":0.0,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142701827","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}
Pub Date : 2024-11-02DOI: 10.1016/j.addicn.2024.100185
Graydon B. Gereau , Diana Zhou , Kalynn Van Voorhies , Ryan E. Tyler , Jeffrey Campbell , Jackson G. Murray , Ali Alvarez-Pamir , Luke A. Wykoff , Michel A. Companion , Michael R. Jackson , Steven H. Olson , Lawrence S. Barak , Lauren M. Slosky , Ryan P. Vetreno , Joyce Besheer , Zoe A. McElligott
Alcohol use disorders (AUDs) impose an enormous societal and financial burden, and world-wide, alcohol misuse is the 7th leading cause of premature death [1]. Despite this, there are currently only 3 FDA approved pharmacological approaches for the treatment of AUDs in the United States. The neurotensin (Nts) system has long been implicated in modulating behaviors associated with alcohol misuse. Recently, a novel compound, SBI-553, that biases the action of Nts receptor 1 (NTSR1) activation, has shown promise in preclinical models of psychostimulant use. Here we investigate the efficacy of this compound to alter ethanol-mediated behaviors in a comprehensive battery of experiments assessing ethanol consumption, behavioral responses to ethanol, physiological sensitivity to ethanol, and ethanol metabolism. Additionally, we investigated behavior in avoidance and cognitive assays to monitor potential side effects of SBI-553. We find that SBI-553 reduces ethanol consumption in mice without altering avoidance behavior or novel object recognition. We also observe sex-dependent differences in physiological responses to sequential ethanol injections in mice. In rats, we show that SBI-553 attenuates sensitivity to the interoceptive effects of ethanol (using a Pavlovian drug discrimination task). Our data suggest that targeting NTSR1 signaling may be promising to attenuate alcohol misuse, and adds to a body of literature that suggests NTSR1 may be a common downstream target involved in the psychoactive effects of multiple reinforcing substances.
{"title":"Biased allosteric modulator of neurotensin receptor 1 reduces ethanol drinking and responses to ethanol administration in rodents","authors":"Graydon B. Gereau , Diana Zhou , Kalynn Van Voorhies , Ryan E. Tyler , Jeffrey Campbell , Jackson G. Murray , Ali Alvarez-Pamir , Luke A. Wykoff , Michel A. Companion , Michael R. Jackson , Steven H. Olson , Lawrence S. Barak , Lauren M. Slosky , Ryan P. Vetreno , Joyce Besheer , Zoe A. McElligott","doi":"10.1016/j.addicn.2024.100185","DOIUrl":"10.1016/j.addicn.2024.100185","url":null,"abstract":"<div><div>Alcohol use disorders (AUDs) impose an enormous societal and financial burden, and world-wide, alcohol misuse is the 7th leading cause of premature death [<span><span>1</span></span>]. Despite this, there are currently only 3 FDA approved pharmacological approaches for the treatment of AUDs in the United States. The neurotensin (Nts) system has long been implicated in modulating behaviors associated with alcohol misuse. Recently, a novel compound, SBI-553, that biases the action of Nts receptor 1 (NTSR1) activation, has shown promise in preclinical models of psychostimulant use. Here we investigate the efficacy of this compound to alter ethanol-mediated behaviors in a comprehensive battery of experiments assessing ethanol consumption, behavioral responses to ethanol, physiological sensitivity to ethanol, and ethanol metabolism. Additionally, we investigated behavior in avoidance and cognitive assays to monitor potential side effects of SBI-553. We find that SBI-553 reduces ethanol consumption in mice without altering avoidance behavior or novel object recognition. We also observe sex-dependent differences in physiological responses to sequential ethanol injections in mice. In rats, we show that SBI-553 attenuates sensitivity to the interoceptive effects of ethanol (using a Pavlovian drug discrimination task). Our data suggest that targeting NTSR1 signaling may be promising to attenuate alcohol misuse, and adds to a body of literature that suggests NTSR1 may be a common downstream target involved in the psychoactive effects of multiple reinforcing substances.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"13 ","pages":"Article 100185"},"PeriodicalIF":0.0,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653382","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}