GeneSet Information

Tier IV GS400125 • Cocaine vs. Saline (Empty): H3Q5dop in the ventral tegmental area contributes to cocaine-mediated rat gene expression (RNA-seq)

from Publication Assignment: 484


Differentially expressed genes in male Sprague-Dawley rats (300-375 g or 250-300 g) following cocaine administration. Gene expression was evaluated via RNA-seq. Data taken from Supplemental Table S1 (associated with Fig 2. E-F and H). Values presented are p-values. Data available at GEO with accession number GSE124055.


Cocaine vs. Saline (Empty)









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


Dopaminylation of histone H3 in ventral tegmental area regulates cocaine seeking.


Science (New York, N.Y.) 04 2020, Vol 368, pp. 197-201


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. PUBMED: 32273471
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Annotation Information

response to cocaine trait (VT:0010718)
response to addictive substance trait (VT:0010488)
response to xenobiotic stimulus trait (VT:0010487)
organism trait (VT:0010454)
ventral tegmental area (UBERON:0002691)

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