» Articles » PMID: 27573876

Dependence-induced Increase of Alcohol Self-administration and Compulsive Drinking Mediated by the Histone Methyltransferase PRDM2

Overview
Journal Mol Psychiatry
Date 2016 Aug 31
PMID 27573876
Citations 29
Authors
Affiliations
Soon will be listed here.
Abstract

Epigenetic processes have been implicated in the pathophysiology of alcohol dependence, but the specific molecular mechanisms mediating dependence-induced neuroadaptations remain largely unknown. Here, we found that a history of alcohol dependence persistently decreased the expression of Prdm2, a histone methyltransferase that monomethylates histone 3 at the lysine 9 residue (H3K9me1), in the rat dorsomedial prefrontal cortex (dmPFC). Downregulation of Prdm2 was associated with decreased H3K9me1, supporting that changes in Prdm2 mRNA levels affected its activity. Chromatin immunoprecipitation followed by massively parallel DNA sequencing showed that genes involved in synaptic communication are epigenetically regulated by H3K9me1 in dependent rats. In non-dependent rats, viral-vector-mediated knockdown of Prdm2 in the dmPFC resulted in expression changes similar to those observed following a history of alcohol dependence. Prdm2 knockdown resulted in increased alcohol self-administration, increased aversion-resistant alcohol intake and enhanced stress-induced relapse to alcohol seeking, a phenocopy of postdependent rats. Collectively, these results identify a novel epigenetic mechanism that contributes to the development of alcohol-seeking behavior following a history of dependence.

Citing Articles

How life events may confer vulnerability to addiction: the role of epigenetics.

Liu S, Harris A, Gewirtz J Front Mol Neurosci. 2024; 17:1462769.

PMID: 39359689 PMC: 11446245. DOI: 10.3389/fnmol.2024.1462769.


Identification of Schizophrenia Susceptibility Loci in the Urban Taiwanese Population.

Huang C, Wang Y, Hsu C, Yeh T, Chang W, Singh A Medicina (Kaunas). 2024; 60(8).

PMID: 39202552 PMC: 11356138. DOI: 10.3390/medicina60081271.


Adolescent binge ethanol impacts H3K9me3-occupancy at synaptic genes and the regulation of oligodendrocyte development.

Brocato E, Easter R, Morgan A, Kakani M, Lee G, Wolstenholme J Front Mol Neurosci. 2024; 17:1389100.

PMID: 38840776 PMC: 11150558. DOI: 10.3389/fnmol.2024.1389100.


Pre- and postsynaptic signatures in the prelimbic cortex associated with "alcohol use disorder" in the rat.

Domi A, Cadeddu D, Lucente E, Gobbo F, Edvardsson C, Petrella M Neuropsychopharmacology. 2024; 49(12):1851-1860.

PMID: 38755284 PMC: 11473806. DOI: 10.1038/s41386-024-01887-2.


Epigenetic drugs and psychedelics as emerging therapies for alcohol use disorder: insights from preclinical studies.

Hilal F, Jeanblanc J, Deschamps C, Naassila M, Pierrefiche O, Ben Hamida S J Neural Transm (Vienna). 2024; 131(5):525-561.

PMID: 38554193 DOI: 10.1007/s00702-024-02757-3.


References
1.
Roberts A, Heyser C, Cole M, Griffin P, Koob G . Excessive ethanol drinking following a history of dependence: animal model of allostasis. Neuropsychopharmacology. 2000; 22(6):581-94. DOI: 10.1016/S0893-133X(99)00167-0. View

2.
Cippitelli A, Karlsson C, Shaw J, Thorsell A, Gehlert D, Heilig M . Suppression of alcohol self-administration and reinstatement of alcohol seeking by melanin-concentrating hormone receptor 1 (MCH1-R) antagonism in Wistar rats. Psychopharmacology (Berl). 2010; 211(4):367-75. DOI: 10.1007/s00213-010-1891-y. View

3.
Deroche-Gamonet V, Belin D, Piazza P . Evidence for addiction-like behavior in the rat. Science. 2004; 305(5686):1014-7. DOI: 10.1126/science.1099020. View

4.
Wolffgramm J, Galli G, Thimm F, Heyne A . Animal models of addiction: models for therapeutic strategies?. J Neural Transm (Vienna). 2000; 107(6):649-68. DOI: 10.1007/s007020070067. View

5.
Geiss G, Bumgarner R, Birditt B, Dahl T, Dowidar N, Dunaway D . Direct multiplexed measurement of gene expression with color-coded probe pairs. Nat Biotechnol. 2008; 26(3):317-25. DOI: 10.1038/nbt1385. View