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Transcriptional control of nucleus accumbens neuronal excitability by retinoid X receptor alpha tunes sensitivity to drug rewards.
Godino, Arthur; Salery, Marine; Durand-de Cuttoli, Romain; Estill, Molly S; Holt, Leanne M; Futamura, Rita; Browne, Caleb J; Mews, Philipp; Hamilton, Peter J; Neve, Rachael L; Shen, Li; Russo, Scott J; Nestler, Eric J.
Afiliación
  • Godino A; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Salery M; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Durand-de Cuttoli R; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Estill MS; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Holt LM; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Futamura R; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Browne CJ; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Mews P; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Hamilton PJ; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Neve RL; Gene Delivery Technology Core, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Shen L; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Russo SJ; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Nestler EJ; Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: eric.nestler@mssm.edu.
Neuron ; 111(9): 1453-1467.e7, 2023 05 03.
Article en En | MEDLINE | ID: mdl-36889314
The complex nature of the transcriptional networks underlying addictive behaviors suggests intricate cooperation between diverse gene regulation mechanisms that go beyond canonical activity-dependent pathways. Here, we implicate in this process a nuclear receptor transcription factor, retinoid X receptor alpha (RXRα), which we initially identified bioinformatically as associated with addiction-like behaviors. In the nucleus accumbens (NAc) of male and female mice, we show that although its own expression remains unaltered after cocaine exposure, RXRα controls plasticity- and addiction-relevant transcriptional programs in both dopamine receptor D1- and D2-expressing medium spiny neurons, which in turn modulate intrinsic excitability and synaptic activity of these NAc cell types. Behaviorally, bidirectional viral and pharmacological manipulation of RXRα regulates drug reward sensitivity in both non-operant and operant paradigms. Together, this study demonstrates a key role for NAc RXRα in promoting drug addiction and paves the way for future studies of rexinoid signaling in psychiatric disease states.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Cocaína / Trastornos Mentales Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Animals Idioma: En Revista: Neuron Asunto de la revista: NEUROLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Cocaína / Trastornos Mentales Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Animals Idioma: En Revista: Neuron Asunto de la revista: NEUROLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos