Kappa Opioid Receptors in Mesolimbic Terminals Mediate Escalation of Cocaine Consumption.
العنوان: | Kappa Opioid Receptors in Mesolimbic Terminals Mediate Escalation of Cocaine Consumption. |
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المؤلفون: | Gordon-Fennell L; Graduate Program in Neuroscience, University of Washington, Seattle, WA 98195.; Center for Neurobiology of Addiction, Pain & Emotion, University of Washington, Seattle, WA 98195.; Department of Psychiatry & Behavioral Science, University of Washington, Seattle, WA 98195., Farero RD; Graduate Program in Neuroscience, University of Washington, Seattle, WA 98195.; Center for Neurobiology of Addiction, Pain & Emotion, University of Washington, Seattle, WA 98195.; Department of Psychiatry & Behavioral Science, University of Washington, Seattle, WA 98195., Burgeno LM; Center for Neurobiology of Addiction, Pain & Emotion, University of Washington, Seattle, WA 98195.; Department of Psychiatry & Behavioral Science, University of Washington, Seattle, WA 98195.; Department of Pharmacology, University of Washington, Seattle, WA 98195., Murray NL; Center for Neurobiology of Addiction, Pain & Emotion, University of Washington, Seattle, WA 98195.; Department of Psychiatry & Behavioral Science, University of Washington, Seattle, WA 98195., Abraham AD; Center for Neurobiology of Addiction, Pain & Emotion, University of Washington, Seattle, WA 98195.; Department of Pharmacology, University of Washington, Seattle, WA 98195., Soden ME; Center for Neurobiology of Addiction, Pain & Emotion, University of Washington, Seattle, WA 98195.; Department of Pharmacology, University of Washington, Seattle, WA 98195., Stuber GD; Graduate Program in Neuroscience, University of Washington, Seattle, WA 98195.; Center for Neurobiology of Addiction, Pain & Emotion, University of Washington, Seattle, WA 98195.; Department of Psychiatry & Behavioral Science, University of Washington, Seattle, WA 98195.; Department of Pharmacology, University of Washington, Seattle, WA 98195.; Department of Anesthesiology & Pain Medicine, University of Washington, Seattle, WA 98195., Chavkin C; Graduate Program in Neuroscience, University of Washington, Seattle, WA 98195.; Center for Neurobiology of Addiction, Pain & Emotion, University of Washington, Seattle, WA 98195.; Department of Pharmacology, University of Washington, Seattle, WA 98195., Zweifel LS; Graduate Program in Neuroscience, University of Washington, Seattle, WA 98195.; Center for Neurobiology of Addiction, Pain & Emotion, University of Washington, Seattle, WA 98195.; Department of Psychiatry & Behavioral Science, University of Washington, Seattle, WA 98195.; Department of Pharmacology, University of Washington, Seattle, WA 98195., Phillips PEM; Graduate Program in Neuroscience, University of Washington, Seattle, WA 98195.; Center for Neurobiology of Addiction, Pain & Emotion, University of Washington, Seattle, WA 98195.; Department of Psychiatry & Behavioral Science, University of Washington, Seattle, WA 98195.; Department of Pharmacology, University of Washington, Seattle, WA 98195. |
المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2023 Dec 23. Date of Electronic Publication: 2023 Dec 23. |
نوع المنشور: | Preprint |
اللغة: | English |
بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
مستخلص: | Increases in drug consumption over time, also known as escalation, is a key behavioral component of substance use disorder (SUD) that is related to potential harm to users, such as overdose. Studying escalation also allows researchers to investigate the transition from casual drug use to more SUD-like drug use. Understanding the neurobiological systems that drive this transition will inform therapeutic treatments in the aim to prevent increases in drug use and the development of SUD. The kappa opioid receptor (KOR) system is typically known for its role in negative affect, which is commonly found in SUD as well. Furthermore, the KOR system has also been implicated in drug use and importantly, modulating the negative effects of drug use. However, the specific neuronal subpopulation expressing KOR involved has not been identified. Here, we first demonstrated that pharmacologically inhibiting KOR in the nucleus accumbens core (NAcC), as a whole, blocks cocaine escalation under long-access self-administration conditions. We then demonstrated that KOR expressed on ventral tegmental area (VTA) neurons but not NAcC neurons is sufficient for blocking cocaine escalation by utilizing a novel virally-mediated CRISPR-SaCas9 knock-out of the oprk1 gene. Together, this suggests that activation of KOR on VTA terminals in the NAcC drives the transition to the SUD-like phenotype of escalation of cocaine consumption. |
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معلومات مُعتمدة: | P30 DA048736 United States DA NIDA NIH HHS; R01 DA039687 United States DA NIDA NIH HHS; T32 DA007278 United States DA NIDA NIH HHS; F31 DA048562 United States DA NIDA NIH HHS; R37 DA051686 United States DA NIDA NIH HHS |
تواريخ الأحداث: | Date Created: 20240108 Latest Revision: 20240808 |
رمز التحديث: | 20240808 |
مُعرف محوري في PubMed: | PMC10769440 |
DOI: | 10.1101/2023.12.21.572842 |
PMID: | 38187718 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2692-8205 |
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DOI: | 10.1101/2023.12.21.572842 |