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GIRK Channels Modulate Opioid-Induced Motor Activity in a Cell Type- and Subunit-Dependent Manner.
Kotecki, Lydia; Hearing, Matthew; McCall, Nora M; Marron Fernandez de Velasco, Ezequiel; Pravetoni, Marco; Arora, Devinder; Victoria, Nicole C; Munoz, Michaelanne B; Xia, Zhilian; Slesinger, Paul A; Weaver, C David; Wickman, Kevin.
Afiliación
  • Kotecki L; Department of Pharmacology and.
  • Hearing M; Department of Pharmacology and.
  • McCall NM; Graduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455.
  • Marron Fernandez de Velasco E; Department of Pharmacology and.
  • Pravetoni M; Department of Pharmacology and Minneapolis Medical Research Foundation, Minneapolis, Minnesota 55415.
  • Arora D; Department of Pharmacology and.
  • Victoria NC; Department of Pharmacology and.
  • Munoz MB; Peptide Biology Laboratories, The Salk Institute for Biological Studies, La Jolla, California 92037.
  • Xia Z; Department of Pharmacology and.
  • Slesinger PA; Peptide Biology Laboratories, The Salk Institute for Biological Studies, La Jolla, California 92037, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029, and.
  • Weaver CD; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37235.
  • Wickman K; Department of Pharmacology and Graduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455, wickm002@umn.edu.
J Neurosci ; 35(18): 7131-42, 2015 May 06.
Article en En | MEDLINE | ID: mdl-25948263
G-protein-gated inwardly rectifying K(+) (GIRK/Kir3) channel activation underlies key physiological effects of opioids, including analgesia and dependence. GIRK channel activation has also been implicated in the opioid-induced inhibition of midbrain GABA neurons and consequent disinhibition of dopamine (DA) neurons in the ventral tegmental area (VTA). Drug-induced disinhibition of VTA DA neurons has been linked to reward-related behaviors and underlies opioid-induced motor activation. Here, we demonstrate that mouse VTA GABA neurons express a GIRK channel formed by GIRK1 and GIRK2 subunits. Nevertheless, neither constitutive genetic ablation of Girk1 or Girk2, nor the selective ablation of GIRK channels in GABA neurons, diminished morphine-induced motor activity in mice. Moreover, direct activation of GIRK channels in midbrain GABA neurons did not enhance motor activity. In contrast, genetic manipulations that selectively enhanced or suppressed GIRK channel function in midbrain DA neurons correlated with decreased and increased sensitivity, respectively, to the motor-stimulatory effect of systemic morphine. Collectively, these data support the contention that the unique GIRK channel subtype in VTA DA neurons, the GIRK2/GIRK3 heteromer, regulates the sensitivity of the mouse mesolimbic DA system to drugs with addictive potential.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Canales de Potasio Rectificados Internamente Asociados a la Proteína G / Neuronas Dopaminérgicas / Neuronas GABAérgicas / Analgésicos Opioides / Actividad Motora Límite: Animals Idioma: En Revista: J Neurosci Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Canales de Potasio Rectificados Internamente Asociados a la Proteína G / Neuronas Dopaminérgicas / Neuronas GABAérgicas / Analgésicos Opioides / Actividad Motora Límite: Animals Idioma: En Revista: J Neurosci Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos