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Histone H3 dopaminylation in ventral tegmental area underlies heroin-induced maladaptive plasticity

ABSTRACT: Persistent transcriptional events in ventral tegmental area (VTA) and other reward relevant brain regions contribute to enduring behavioral adaptations that characterize substance use disorder (SUD). 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. In rats undergoing abstinence from heroin self-administration (SA), we found acute and persistent accumulation of H3Q5dop in VTA. By attenuating H3Q5dop during abstinence, we both altered gene expression programs associated with heroin withdrawal and reduced heroin-primed reinstatement behavior. These findings thus establish an essential role for H3Q5dop, and its downstream transcriptional consequences, in opioid-induced plasticity in VTA.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE169628 | GEO | 2022/02/20

REPOSITORIES: GEO

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Dopaminylation of Histone H3 in Ventral Tegmental Area Regulates Cocaine-seeking

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Histone H3 dopaminylation in nucleus accumbens, but not medial prefrontal cortex, contributes to cocaine-seeking following prolonged abstinence

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Histone H3 dopaminylation in ventral tegmental area underlies heroin-induced maladaptive plasticity

Project description:Histone H3 dopaminylation in ventral tegmental area underlies heroin-induced maladaptive plasticity

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Rat medial prefrontal cortex gene expression following heroin self-administration, abstinence, and extinction

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small-RNA sequencing after 2 days forced abstinence from heroin or sucrose self-administration in male rats

Project description:We report the miRNAs differentially expressed in the orbitofrontal cortex of adult male rats that self-administered heroin after 2 days of forced abstinence.

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2021-01-28 | PXD019485 | Pride

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