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α6 subunit-containing nicotinic receptors mediate low-dose ethanol effects on ventral tegmental area neurons and ethanol reward.
Steffensen, Scott C; Shin, Samuel I; Nelson, Ashley C; Pistorius, Stephanie S; Williams, Stephanie B; Woodward, Taylor J; Park, Hyun Jung; Friend, Lindsey; Gao, Ming; Gao, Fenfei; Taylor, Devin H; Foster Olive, M; Edwards, Jeffrey G; Sudweeks, Sterling N; Buhlman, Lori M; Michael McIntosh, J; Wu, Jie.
Afiliación
  • Steffensen SC; Department of Psychology and Neuroscience, Brigham Young University, Provo, UT, USA.
  • Shin SI; Department of Psychology and Neuroscience, Brigham Young University, Provo, UT, USA.
  • Nelson AC; Department of Psychology and Neuroscience, Brigham Young University, Provo, UT, USA.
  • Pistorius SS; Department of Psychology and Neuroscience, Brigham Young University, Provo, UT, USA.
  • Williams SB; Department of Psychology and Neuroscience, Brigham Young University, Provo, UT, USA.
  • Woodward TJ; Department of Psychology and Neuroscience, Brigham Young University, Provo, UT, USA.
  • Park HJ; Department of Psychology and Neuroscience, Brigham Young University, Provo, UT, USA.
  • Friend L; Department of Psychology and Neuroscience, Brigham Young University, Provo, UT, USA.
  • Gao M; Department of Neurobiology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
  • Gao F; Department of Neurobiology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
  • Taylor DH; Utah Valley University, Orem, UT, USA.
  • Foster Olive M; School of Psychology, Arizona State University, Tempe, AZ, USA.
  • Edwards JG; Department of Psychology and Neuroscience, Brigham Young University, Provo, UT, USA.
  • Sudweeks SN; Department of Psychology and Neuroscience, Brigham Young University, Provo, UT, USA.
  • Buhlman LM; Biomedical Sciences Program, Midwestern University, Glendale, AZ, USA.
  • Michael McIntosh J; Departments of Psychiatry and Biology, University of Utah, Salt Lake City, UT, USA.
  • Wu J; Department of Neurobiology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
Addict Biol ; 23(5): 1079-1093, 2018 09.
Article en En | MEDLINE | ID: mdl-28901722
Dopamine (DA) neuron excitability is regulated by inhibitory GABAergic synaptic transmission and modulated by nicotinic acetylcholine receptors (nAChRs). The aim of this study was to evaluate the role of α6 subunit-containing nAChRs (α6*-nAChRs) in acute ethanol effects on ventral tegmental area (VTA) GABA and DA neurons. α6*-nAChRs were visualized on GABA terminals on VTA GABA neurons, and α6*-nAChR transcripts were expressed in most DA neurons, but only a minority of VTA GABA neurons from GAD67 GFP mice. Low concentrations of ethanol (1-10 mM) enhanced GABAA receptor (GABAA R)-mediated spontaneous and evoked inhibition with blockade by selective α6*-nAChR antagonist α-conotoxins (α-Ctxs) and lowered sensitivity in α6 knock-out (KO) mice. Ethanol suppression of VTA GABA neuron firing rate in wild-type mice in vivo was significantly reduced in α6 KO mice. Ethanol (5-100 mM) had no effect on optically evoked GABAA R-mediated inhibition of DA neurons, and ethanol enhancement of VTA DA neuron firing rate at high concentrations was not affected by α-Ctxs. Ethanol conditioned place preference was reduced in α6 KO mice compared with wild-type controls. Taken together, these studies indicate that relatively low concentrations of ethanol act through α6*-nAChRs on GABA terminals to enhance GABA release onto VTA GABA neurons, in turn to reduce GABA neuron firing, which may lead to VTA DA neuron disinhibition, suggesting a possible mechanism of action of alcohol and nicotine co-abuse.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Recompensa / Receptores Nicotínicos / Área Tegmental Ventral / Etanol / Neuronas GABAérgicas Límite: Animals Idioma: En Revista: Addict Biol Asunto de la revista: TRANSTORNOS RELACIONADOS COM SUBSTANCIAS Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Recompensa / Receptores Nicotínicos / Área Tegmental Ventral / Etanol / Neuronas GABAérgicas Límite: Animals Idioma: En Revista: Addict Biol Asunto de la revista: TRANSTORNOS RELACIONADOS COM SUBSTANCIAS Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos