Dopaminylation of histone H3 in ventral tegmental area regulates cocaine seeking

Author:

Lepack Ashley E.1ORCID,Werner Craig T.2ORCID,Stewart Andrew F.1ORCID,Fulton Sasha L.1,Zhong Ping3ORCID,Farrelly Lorna A.1,Smith Alexander C. W.1ORCID,Ramakrishnan Aarthi1ORCID,Lyu Yang1ORCID,Bastle Ryan M.1ORCID,Martin Jennifer A.2ORCID,Mitra Swarup2,O’Connor Richard M.1,Wang Zi-Jun3,Molina Henrik4ORCID,Turecki Gustavo5,Shen Li1ORCID,Yan Zhen3ORCID,Calipari Erin S.6ORCID,Dietz David M.2ORCID,Kenny Paul J.1,Maze Ian17ORCID

Affiliation:

1. Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

2. Department of Pharmacology and Toxicology, Program in Neuroscience, State University of New York at Buffalo, Buffalo, NY 14214, USA.

3. Department of Physiology and Biophysics, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14203, USA.

4. Proteomics Resource Center, The Rockefeller University, New York, NY 10065, USA.

5. Department of Psychiatry, McGill University, Montreal, QC H3A 1A1, Canada.

6. Department of Pharmacology, Center for Addiction Research, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.

7. Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Abstract

More than a normal neurotransmitter The molecular mechanisms underlying the persistence of addiction remain largely unclear. Lepack et al. found that, with cocaine exposure, there is an intracellular accumulation of dopamine in neurons of a brain region called the ventral tegmental area (see the Perspective by Girault). Dopamine associates with chromatin to initiate a previously unknown form of epigenetic regulation called dopaminylation. This modification has an impact on ventral tegmental area function and, consequently, on dopaminergic action potentials. The result is aberrant dopamine signaling in the ventral striatum during periods of drug seeking. Science , this issue p. 197 ; see also p. 134

Funder

National Institute of Mental Health

National Institute on Drug Abuse

National Institute of Neurological Disorders and Stroke

Brain and Behavior Research Foundation

Whitehall Foundation

Edward Mallinckrodt, Jr. Foundation

Alfred P. Sloan Foundation

Brain Research Foundation

MQ Mental Health Charity

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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