The First Alcohol Drink Triggers mTORC1-Dependent Synaptic Plasticity in Nucleus Accumbens Dopamine D1 Receptor Neurons

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Jacob T BeckleyDorit Ron

Abstract

Early binge-like alcohol drinking may promote the development of hazardous intake. However, the enduring cellular alterations following the first experience with alcohol consumption are not fully understood. We found that the first binge-drinking alcohol session produced enduring enhancement of excitatory synaptic transmission onto dopamine D1 receptor-expressing neurons (D1+ neurons) in the nucleus accumbens (NAc) shell but not the core in mice, which required D1 receptors (D1Rs) and mechanistic target of rapamycin complex 1 (mTORC1). Furthermore, inhibition of mTORC1 activity during the first alcohol drinking session reduced alcohol consumption and preference of a subsequent drinking session. mTORC1 is critically involved in RNA-to-protein translation, and we found that the first alcohol session rapidly activated mTORC1 in NAc shell D1+ neurons and increased synaptic expression of the AMPAR subunit GluA1 and the scaffolding protein Homer. Finally, D1R stimulation alone was sufficient to activate mTORC1 in the NAc to promote mTORC1-dependent translation of the synaptic proteins GluA1 and Homer. Together, our results indicate that the first alcohol drinking session induces synaptic plasticity in NAc D1+ neurons via enhanced mTO...Continue Reading

Citations

Nov 12, 2016·Life Sciences·Udo Bonnet
Jan 20, 2017·Alcoholism, Clinical and Experimental Research·Scott A WegnerFrederic Woodward Hopf
Dec 3, 2016·Genes, Brain, and Behavior·N Morisot, D Ron
Jul 7, 2017·Addiction Biology·Nadege MorisotDorit Ron
Oct 19, 2017·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Xiaojie LiuQing-Song Liu
Dec 19, 2017·Frontiers in Psychiatry·Valentina CastelliCarla Cannizzaro
Jan 8, 2018·Neurochemical Research·Mickaël Naassila, Olivier Pierrefiche
Jul 5, 2019·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Sophie Laguesse, Dorit Ron
Jun 5, 2019·The European Journal of Neuroscience·Horst SchicknickWolfgang Tischmeyer
Jan 11, 2020·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Jérémie NeastaSami Ben Hamida
Jul 9, 2020·Addiction Biology·Antonio Jesús López-GamberoJuan Suárez
Aug 29, 2020·Journal of Psychopharmacology·Marcos UchaAlejandro Higuera-Matas
Jul 23, 2016·Nature Reviews. Neuroscience·Dorit Ron, Segev Barak
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Feb 16, 2017·European Journal of Nuclear Medicine and Molecular Imaging·Simon KallerOsama Sabri
May 18, 2020·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Yann EhingerDorit Ron
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Jan 27, 2021·Neuroscience and Biobehavioral Reviews·Francesco Fornai, Stefano Puglisi-Allegra
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May 1, 2021·International Journal of Molecular Sciences·Anna K RadkeFrederic W Hopf
Jul 23, 2019·Journal of Proteome Research·Phillip StarskiDoo-Sup Choi

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