GeneSet Information

Tier IV GS408306 • Differential gene expression in ventral tegmental area of rats with heroin self-administration_FDR_subset0.05

DESCRIPTION:

Subset of GS407907 for only differentially expressed genes at FDR < 0.05.

LABEL:

Heroin_rat_ventral tegmental area_FDR_subset0.05

SCORE TYPE:

Q-Value

DATE ADDED:

2024-03-14

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Sasha L Fulton, Swarup Mitra, Ashley E Lepack, Jennifer A Martin, Andrew F Stewart, Jacob Converse, Mason Hochstetler, David M Dietz, Ian Maze

TITLE:

Histone H3 dopaminylation in ventral tegmental area underlies heroin-induced transcriptional and behavioral plasticity in male rats.

JOURNAL:

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology Sep 2022, Vol 47, pp. 1776-1783

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. 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. PUBMED: 35094023
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Annotation Information

No sequence read archive data associated with this GeneSet.


Brain (D001921)
Laboratories (D007753)
Behavior (D001519)
Gene Expression (D015870)
Role (D012380)
Glutamine (D005973)
Rats (D051381)
Ventral Tegmental Area (D017557)
Genes (D005796)
Cocaine (D003042)
Heroin (D003932)
Reward (D012201)
Programs (D019542)
midbrain (MA:0000207)
brain (MA:0000168)
post-translational protein modification (GO:0043687)
gene expression (GO:0010467)
behavior (GO:0007610)
signaling (GO:0023052)
Operation (EDAM_operation:0004)
Genetics (EDAM_topic:3053)
Transcriptomics (EDAM_topic:0203)
Data (EDAM_data:0006)
Pathways, networks and models (EDAM_topic:0602)
heroin (CHEBI:27808)
L-glutamine (CHEBI:18050)
cocaine (CHEBI:27958)
cocaine(1+) (CHEBI:60056)
drug (CHEBI:23888)
glutamine (CHEBI:28300)
role (CHEBI:50906)
histone (CHEBI:15358)
Acute (HP:0011009)
disease (EFO:0000408)
disease recurrence (EFO:0004952)
ventral (EFO:0001662)
area (EFO:0001696)
obsolete_ventral tegmental area (EFO:0001935)
rostral octaval nerve motor nucleus (UBERON:2002175)
midbrain (UBERON:0001891)
brain (UBERON:0000955)
ventral tegmental area (UBERON:0002691)
postsubiculum (UBERON:0035971)
adult cerebral ganglion (UBERON:6110636)

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Supported by NIH R01 AA18776 jointly funded by NIAAA and NIDA, and JAX Center for Precision Genetics NIH U54 OD 020351