Histone H3 dopaminylation in ventral tegmental area underlies heroin-induced transcriptional and behavioral plasticity in male rats.
Histone H3 dopaminylation in ventral tegmental area underlies heroin-induced transcriptional and behavioral plasticity in male rats.
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DOI：
10.1038/s41386-022-01279-4
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发表时间：
2022-09
影响因子：
7.6
通讯作者：
Maze, Ian
中科院分区：
文献类型：
--
作者：
Fulton, Sasha L.;Mitra, Swarup;Lepack, Ashley E.;Martin, Jennifer A.;Stewart, Andrew F.;Converse, Jacob;Hochstetler, Mason;Dietz, David M.;Maze, Ian
Persistent transcriptional events in ventral tegmental area (VTA) and other reward relevant brain regions contribute to enduring behavioral adaptations that characterize substance use disorder. Recent data from our laboratory indicate that aberrant accumulation of the newly discovered histone post-translational modification (PTM), H3 dopaminylation at glutamine 5 (H3Q5dop), contributes significantly to cocaine-seeking behavior following prolonged periods of abstinence. It remained unclear, however, whether this modification is important for relapse vulnerability in the context of other drugs of abuse, such as opioids. Here, we showed that H3Q5dop plays a critical role in heroin-mediated transcriptional plasticity in midbrain regions, particularly the VTA. In rats undergoing abstinence from heroin self-administration (SA), we found acute and persistent accumulation of H3Q5dop in VTA. Attenuation of H3Q5dop during abstinence induced persistent changes in gene expression programs associated with neuronal signaling and dopaminergic function in heroin abstinence and led to reduced heroin-seeking behavior. Interestingly, the observed changes in molecular pathways after heroin SA showed significant yet reversed overlap with the same genes altered in cocaine SA. These findings establish an essential role for H3Q5dop, and its downstream transcriptional consequences, in heroin-induced functional plasticity in VTA.
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影响因子：
25
作者：
Habib, Naomi;McCabe, Cristin;Medina, Sedi;Varshavsky, Miriam;Kitsberg, Daniel;Dvir-Szternfeld, Raz;Green, Gilad;Dionne, Danielle;Nguyen, Lan;Marshall, Jamie L.;Chen, Fei;Zhang, Feng;Kaplan, Tommy;Regev, Aviv;Schwartz, Michal
通讯作者：
Schwartz, Michal
影响因子：
4.6
作者：
Cahill KM;Huo Z;Tseng GC;Logan RW;Seney ML
通讯作者：
Seney ML
影响因子：
16.6
作者：
Martin, Jennifer A.;Werner, Craig T.;Dietz, David M.
通讯作者：
Dietz, David M.
影响因子：
12.4
作者：
Reimsnider, Sharon;Manfredsson, Fredric P.;Mandel, Ronald J.
通讯作者：
Mandel, Ronald J.
影响因子：
5.3
作者：
Nestler, EJ
通讯作者：
Nestler, EJ