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

Overview

Journal Mol Psychiatry

Specialties Molecular Biology
Psychiatry

Date 2016 Aug 31

PMID 27573876

Citations 29

Authors

E Barbier

A L Johnstone

B B Khomtchouk

J D Tapocik

C Pitcairn

F Rehman

E Augier

A Borich

J R Schank

C A Rienas

D J Van Booven

H Sun

D Natt

C Wahlestedt

M Heilig

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.

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References

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

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

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

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

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

Meinhardt M, Sommer W . Postdependent state in rats as a model for medication development in alcoholism. Addict Biol. 2014; 20(1):1-21. DOI: 10.1111/adb.12187. View

Frank T, Rutherford M, Strenzke N, Neef A, Pangrsic T, Khimich D . Bassoon and the synaptic ribbon organize Ca²+ channels and vesicles to add release sites and promote refilling. Neuron. 2010; 68(4):724-38. PMC: 3005353. DOI: 10.1016/j.neuron.2010.10.027. View

Wang J, Duncan D, Shi Z, Zhang B . WEB-based GEne SeT AnaLysis Toolkit (WebGestalt): update 2013. Nucleic Acids Res. 2013; 41(Web Server issue):W77-83. PMC: 3692109. DOI: 10.1093/nar/gkt439. View

Le A, Shaham Y . Neurobiology of relapse to alcohol in rats. Pharmacol Ther. 2002; 94(1-2):137-56. DOI: 10.1016/s0163-7258(02)00200-0. View

10.

Sakharkar A, Zhang H, Tang L, Baxstrom K, Shi G, Moonat S . Effects of histone deacetylase inhibitors on amygdaloid histone acetylation and neuropeptide Y expression: a role in anxiety-like and alcohol-drinking behaviours. Int J Neuropsychopharmacol. 2014; 17(8):1207-20. PMC: 4140694. DOI: 10.1017/S1461145714000054. View

11.

Macey D, Schulteis G, Heinrichs S, Koob G . Time-dependent quantifiable withdrawal from ethanol in the rat: effect of method of dependence induction. Alcohol. 1996; 13(2):163-70. DOI: 10.1016/0741-8329(95)02030-6. View

12.

Epstein D, Preston K, Stewart J, Shaham Y . Toward a model of drug relapse: an assessment of the validity of the reinstatement procedure. Psychopharmacology (Berl). 2006; 189(1):1-16. PMC: 1618790. DOI: 10.1007/s00213-006-0529-6. View

13.

Vendruscolo L, Barbier E, Schlosburg J, Misra K, Whitfield Jr T, Logrip M . Corticosteroid-dependent plasticity mediates compulsive alcohol drinking in rats. J Neurosci. 2012; 32(22):7563-71. PMC: 3375621. DOI: 10.1523/JNEUROSCI.0069-12.2012. View

14.

Farris S, Arasappan D, Hunicke-Smith S, Harris R, Mayfield R . Transcriptome organization for chronic alcohol abuse in human brain. Mol Psychiatry. 2014; 20(11):1438-47. PMC: 4452464. DOI: 10.1038/mp.2014.159. View

15.

Watson C, Szutorisz H, Garg P, Martin Q, Landry J, Sharp A . Genome-Wide DNA Methylation Profiling Reveals Epigenetic Changes in the Rat Nucleus Accumbens Associated With Cross-Generational Effects of Adolescent THC Exposure. Neuropsychopharmacology. 2015; 40(13):2993-3005. PMC: 4864634. DOI: 10.1038/npp.2015.155. View

16.

Moonat S, Sakharkar A, Zhang H, Tang L, Pandey S . Aberrant histone deacetylase2-mediated histone modifications and synaptic plasticity in the amygdala predisposes to anxiety and alcoholism. Biol Psychiatry. 2013; 73(8):763-73. PMC: 3718567. DOI: 10.1016/j.biopsych.2013.01.012. View

17.

Finegersh A, Ferguson C, Maxwell S, Mazariegos D, Farrell D, Homanics G . Repeated vapor ethanol exposure induces transient histone modifications in the brain that are modified by genotype and brain region. Front Mol Neurosci. 2015; 8:39. PMC: 4524924. DOI: 10.3389/fnmol.2015.00039. View

18.

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

19.

Bilang-Bleuel A, Ulbricht S, Chandramohan Y, De Carli S, Droste S, Reul J . Psychological stress increases histone H3 phosphorylation in adult dentate gyrus granule neurons: involvement in a glucocorticoid receptor-dependent behavioural response. Eur J Neurosci. 2005; 22(7):1691-700. DOI: 10.1111/j.1460-9568.2005.04358.x. View

20.

Liu J, Lewohl J, Harris R, Dodd P, Mayfield R . Altered gene expression profiles in the frontal cortex of cirrhotic alcoholics. Alcohol Clin Exp Res. 2007; 31(9):1460-6. DOI: 10.1111/j.1530-0277.2007.00444.x. View