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A Cocaine-Activated Ensemble Exerts Increased Control Over Behavior While Decreasing in Size.

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العنوان: A Cocaine-Activated Ensemble Exerts Increased Control Over Behavior While Decreasing in Size.
المؤلفون: Thibeault KC; Vanderbilt Brain Institute, Vanderbilt University, Nashville, Tennessee; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, Tennessee., Leonard MZ; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, Tennessee; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee., Kondev V; Vanderbilt Brain Institute, Vanderbilt University, Nashville, Tennessee; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, Tennessee., Emerson SD; Vanderbilt Brain Institute, Vanderbilt University, Nashville, Tennessee; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, Tennessee., Bethi R; Vanderbilt Brain Institute, Vanderbilt University, Nashville, Tennessee; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, Tennessee., Lopez AJ; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, Tennessee; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee., Sens JP; Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina., Nabit BP; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, Tennessee; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee., Elam HB; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, Tennessee; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee., Winder DG; Vanderbilt Brain Institute, Vanderbilt University, Nashville, Tennessee; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, Tennessee; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee; Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, Tennessee; Vanderbilt JF Kennedy Center, Vanderbilt University School of Medicine, Nashville, Tennessee., Patel S; Department of Psychiatry, Northwestern University, Chicago, Illinois., Kiraly DD; Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina., Grueter BA; Vanderbilt Brain Institute, Vanderbilt University, Nashville, Tennessee; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, Tennessee; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee; Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, Tennessee., Calipari ES; Vanderbilt Brain Institute, Vanderbilt University, Nashville, Tennessee; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, Tennessee; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee; Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, Tennessee; Vanderbilt JF Kennedy Center, Vanderbilt University School of Medicine, Nashville, Tennessee. Electronic address: erin.calipari@vanderbilt.edu.
المصدر: Biological psychiatry [Biol Psychiatry] 2024 Jun 18. Date of Electronic Publication: 2024 Jun 18.
Publication Model: Ahead of Print
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: United States NLM ID: 0213264 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2402 (Electronic) Linking ISSN: 00063223 NLM ISO Abbreviation: Biol Psychiatry Subsets: MEDLINE
أسماء مطبوعة: Publication: New York, NY : Elsevier
Original Publication: New York, Plenum Pub. Corp.
مستخلص: Background: Substance use disorder is characterized by long-lasting changes in reward-related brain regions, such as the nucleus accumbens. Previous work has shown that cocaine exposure induces plasticity in broad, genetically defined cell types in the nucleus accumbens; however, in response to a stimulus, only a small percentage of neurons are transcriptionally active-termed an ensemble. Here, we identify an Arc-expressing neuronal ensemble that has a unique trajectory of recruitment and causally controls drug self-administration after repeated, but not acute, cocaine exposure.
Methods: Using Arc-CreER T2 transgenic mice, we expressed transgenes in Arc+ ensembles activated by cocaine exposure (either acute [1 × 10 mg/kg intraperitoneally] or repeated [10 × 10 mg/kg intraperitoneally]). Using genetic, optical, and physiological recording and manipulation strategies, we assessed the contribution of these ensembles to behaviors associated with substance use disorder.
Results: Repeated cocaine exposure reduced the size of the ensemble while simultaneously increasing its control over behavior. Neurons within the repeated cocaine ensemble were hyperexcitable, and their optogenetic excitation was sufficient for reinforcement. Finally, lesioning the repeated cocaine, but not the acute cocaine, ensemble blunted cocaine self-administration. Thus, repeated cocaine exposure reduced the size of the ensemble while simultaneously increasing its contributions to drug reinforcement.
Conclusions: We showed that repeated, but not acute, cocaine exposure induced a physiologically distinct ensemble characterized by the expression of the immediate early gene Arc, which was uniquely capable of modulating reinforcement behavior.
(Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: Addiction; Engram; Operant conditioning; Stimulant; Striatum
تواريخ الأحداث: Date Created: 20240620 Latest Revision: 20240802
رمز التحديث: 20240802
DOI: 10.1016/j.biopsych.2024.06.008
PMID: 38901723
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-2402
DOI:10.1016/j.biopsych.2024.06.008