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Stress Increases Ethanol Self-Administration via a Shift toward Excitatory GABA Signaling in the Ventral Tegmental Area.
Ostroumov, Alexey; Thomas, Alyse M; Kimmey, Blake A; Karsch, Jordan S; Doyon, William M; Dani, John A.
Afiliación
  • Ostroumov A; Department of Neuroscience, Mahoney Institute for Neurosciences, Perelman School for Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Thomas AM; Department of Neuroscience, Mahoney Institute for Neurosciences, Perelman School for Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Kimmey BA; Department of Neuroscience, Mahoney Institute for Neurosciences, Perelman School for Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Karsch JS; Department of Neuroscience, Mahoney Institute for Neurosciences, Perelman School for Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Doyon WM; Department of Neuroscience, Mahoney Institute for Neurosciences, Perelman School for Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Dani JA; Department of Neuroscience, Mahoney Institute for Neurosciences, Perelman School for Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: johndani@upenn.edu.
Neuron ; 92(2): 493-504, 2016 Oct 19.
Article en En | MEDLINE | ID: mdl-27720487
Stress is a well-known risk factor for subsequent alcohol abuse, but the neural mechanisms underlying interactions between stress and alcohol remain largely unknown. Addictive drug reinforcement and stress signaling involve common neural circuitry, including the mesolimbic dopamine system. We demonstrate in rodents that pre-exposure to stress attenuates alcohol-induced dopamine responses and increases alcohol self-administration. The blunted dopamine signaling resulted from ethanol-induced excitation of GABA neurons in the ventral tegmental area. Excitation of GABA neurons was mediated by GABAA receptor activation and involved stress-induced functional downregulation of the K+, Cl- cotransporter, KCC2. Blocking stress hormone receptors, enhancing KCC2 function, or preventing excitatory GABA signaling by alternative methods all prevented the attenuated alcohol-induced dopamine response and prevented the increased alcohol self-administration. These results demonstrate that stress alters the neural and behavioral responses to alcohol through a neuroendocrine signal that shifts inhibitory GABA transmission toward excitation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estrés Psicológico / Autoadministración / Dopamina / Depresores del Sistema Nervioso Central / Área Tegmental Ventral / Etanol / Alcoholismo / Neuronas Dopaminérgicas / Ácido gamma-Aminobutírico Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: Neuron Asunto de la revista: NEUROLOGIA Año: 2016 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: Estrés Psicológico / Autoadministración / Dopamina / Depresores del Sistema Nervioso Central / Área Tegmental Ventral / Etanol / Alcoholismo / Neuronas Dopaminérgicas / Ácido gamma-Aminobutírico Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: Neuron Asunto de la revista: NEUROLOGIA Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos