Dopaminylation of histone H3 in ventral tegmental area regulates cocaine seeking

Science. 2020 Apr 10;368(6487):197-201. doi: 10.1126/science.aaw8806.

Ashley E Lepack 1Craig T Werner 2Andrew F Stewart 1Sasha L Fulton 1Ping Zhong 3Lorna A Farrelly 1Alexander C W Smith 1Aarthi Ramakrishnan 1Yang Lyu 1Ryan M Bastle 1Jennifer A Martin 2Swarup Mitra 2Richard M O’Connor 1Zi-Jun Wang 3Henrik Molina 4Gustavo Turecki 5Li Shen 1Zhen Yan 3Erin S Calipari 6David M Dietz 2Paul J Kenny 1Ian Maze 7 8Affiliations expand

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Abstract

Vulnerability to relapse during periods of attempted abstinence from cocaine use is hypothesized to result from the rewiring of brain reward circuitries, particularly ventral tegmental area (VTA) dopamine neurons. How cocaine exposures act on midbrain dopamine neurons to precipitate addiction-relevant changes in gene expression is unclear. We found that histone H3 glutamine 5 dopaminylation (H3Q5dop) plays a critical role in cocaine-induced transcriptional plasticity in the midbrain. Rats undergoing withdrawal from cocaine showed an accumulation of H3Q5dop in the VTA. By reducing H3Q5dop in the VTA during withdrawal, we reversed cocaine-mediated gene expression changes, attenuated dopamine release in the nucleus accumbens, and reduced cocaine-seeking behavior. These findings establish a neurotransmission-independent role for nuclear dopamine in relapse-related transcriptional plasticity in the VTA.

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About S. R. Zelenz 102 Articles
S.R. Zelenz has worked in education for 20 years. Working with students from all walks of life, cultures, races, and social diversity, Zelenz’s research in Educational Leadership led to finding a better way to approach learning for students with trauma histories. Many were juvenile offenders, gang members, diagnosed with varying behavioral disorders, or had family histories of violence, murder, or narcissistic parenting. This research could not be effectively accomplished without further understanding: how epigenetic trauma inheritance may be impacting these students; how brain development from trauma may be impacting their behavioral and emotional development; as well as deep understanding of psychology and its varying classifications for behavioral and personality disorders. The goal is to find solutions for changing the conversation and making a real difference for these students. She has also worked with nonprofits of varying focus areas for the last 25 years. Her undergraduate degree in Arts Administration and Music prepared her for managing nonprofits of any size as well as procuring funding so that they can achieve their goals. Pairing her nonprofit background with her education background, she has been able to make a difference for over 200 nonprofits worldwide, written curriculum for schools across the globe, and assisted many arts organizations through performance and management.