期刊
SCIENCE
卷 368, 期 6487, 页码 197-+出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aaw8806
关键词
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资金
- National Institutes of Health [DP1 DA042078, R21DA044767, P50 MH096890, RO DA025983, R01 MH108842, R01 DA037257, R21DA044486, F99 NS108543, RODDA04211, F31DA045428]
- MQ Mental Health Research Charity [MQ15FIP100011]
- Alfred P.Sloan Foundation Fellowship in Neuroscience
- Brain Research Foundation's Fay/Frank SeedGrant Award
- Brain and Behavior Research Foundation
- Whitehall Foundation
- EdwardMallinckrodt, Jr. Foundation
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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