دورية أكاديمية

Connexin-36-positive gap junctions in ventral tegmental area GABA neurons sustain opiate dependence.

التفاصيل البيبلوغرافية
العنوان: Connexin-36-positive gap junctions in ventral tegmental area GABA neurons sustain opiate dependence.
المؤلفون: Maal-Bared G; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada., Yee M; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada., Harding EK; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada., Ghebreselassie M; Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada., Bergamini M; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.; Department of Human Biology, University of Toronto, Toronto, Ontario, Canada., Choy R; Department of Human Biology, University of Toronto, Toronto, Ontario, Canada., Kim E; Department of Human Biology, University of Toronto, Toronto, Ontario, Canada., Di Vito S; Department of Human Biology, University of Toronto, Toronto, Ontario, Canada., Patel M; Department of Human Biology, University of Toronto, Toronto, Ontario, Canada., Amirzadeh M; Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada., Grieder TE; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada., Coles BL; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada., Nagy JI; Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada., Bonin RP; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada., Steenland HW; NeuroTek Innovative Technology, Toronto, Ontario, Canada., van der Kooy D; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.; Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
المصدر: The European journal of neuroscience [Eur J Neurosci] 2024 Jun; Vol. 59 (12), pp. 3422-3444. Date of Electronic Publication: 2024 Apr 28.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Wiley-Blackwell Country of Publication: France NLM ID: 8918110 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1460-9568 (Electronic) Linking ISSN: 0953816X NLM ISO Abbreviation: Eur J Neurosci Subsets: MEDLINE
أسماء مطبوعة: Publication: : Oxford : Wiley-Blackwell
Original Publication: Oxford, UK : Published on behalf of the European Neuroscience Association by Oxford University Press, c1989-
مواضيع طبية MeSH: Connexins*/metabolism , Connexins*/genetics , GABAergic Neurons*/metabolism , GABAergic Neurons*/drug effects , Gap Junctions*/metabolism , Gap Junctions*/drug effects , Opioid-Related Disorders*/metabolism , Opioid-Related Disorders*/physiopathology , Ventral Tegmental Area*/metabolism , Ventral Tegmental Area*/drug effects, Animals ; Male ; Mice ; Rats ; Gap Junction delta-2 Protein ; Mefloquine/pharmacology ; Pedunculopontine Tegmental Nucleus/metabolism ; Pedunculopontine Tegmental Nucleus/drug effects ; Rats, Sprague-Dawley
مستخلص: Drug dependence is characterized by a switch in motivation wherein a positively reinforcing substance can become negatively reinforcing. Put differently, drug use can transform from a form of pleasure-seeking to a form of relief-seeking. Ventral tegmental area (VTA) GABA neurons form an anatomical point of divergence between two double dissociable pathways that have been shown to be functionally implicated and necessary for these respective motivations to seek drugs. The tegmental pedunculopontine nucleus (TPP) is necessary for opiate conditioned place preferences (CPP) in previously drug-naïve rats and mice, whereas dopaminergic (DA) transmission in the nucleus accumbens (NAc) is necessary for opiate CPP in opiate-dependent and withdrawn (ODW) rats and mice. Here, we show that this switch in functional anatomy is contingent upon the gap junction-forming protein, connexin-36 (Cx36), in VTA GABA neurons. Intra-VTA infusions of the Cx36 blocker, mefloquine, in ODW rats resulted in a reversion to a drug-naïve-like state wherein the TPP was necessary for opiate CPP and where opiate withdrawal aversions were lost. Consistent with these data, conditional knockout mice lacking Cx36 in GABA neurons (GAD65-Cre;Cx36 fl(CFP)/fl(CFP) ) exhibited a perpetual drug-naïve-like state wherein opiate CPP was always DA independent, and opiate withdrawal aversions were absent even in mice subjected to an opiate dependence and withdrawal induction protocol. Further, viral-mediated rescue of Cx36 in VTA GABA neurons was sufficient to restore their susceptibility to an ODW state wherein opiate CPP was DA dependent. Our findings reveal a functional role for VTA gap junctions that has eluded prevailing circuit models of addiction.
(© 2024 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)
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معلومات مُعتمدة: FDN-148407 Canada CAPMC CIHR; FDN-148407 Canada CAPMC CIHR
فهرسة مساهمة: Keywords: conditioned place preference; genetic rescue; morphine withdrawal; reward
المشرفين على المادة: 0 (Connexins)
0 (Gap Junction delta-2 Protein)
TML814419R (Mefloquine)
تواريخ الأحداث: Date Created: 20240428 Date Completed: 20240614 Latest Revision: 20240926
رمز التحديث: 20240926
DOI: 10.1111/ejn.16366
PMID: 38679044
قاعدة البيانات: MEDLINE
الوصف
تدمد:1460-9568
DOI:10.1111/ejn.16366