Role of histone modifying enzyme PRDM2 in alcohol-related behaviors

Monday, September 22, 2014 — Poster Session I
12:00 p.m. – 2:00 p.m.	FAES Academic Center	NIAAA	NEURO-3

Authors

• E. Barbier
• C. Pitcairn
• A. Borich
• J. Tapocik
• A. Johnstone
• J. Schank
• Z. Zhou
• Q. Yuan
• D. Goldman
• C. Wahlestedt
• M. Heilig

Abstract

Exposing rats to repeated cycles of alcohol intoxication and withdrawal will produce persistent changes in voluntary alcohol consumption. To uncover the neural correlates behind these changes, we wanted to investigate how the expression of epigenetic enzymes is changed following alcohol-exposure and whether these expression differences are associated with behaviors characteristic of post-dependent rats. To test this, alcohol dependence was induced by chronically exposing rats to alcohol vapor. Three weeks after conclusion of alcohol exposure, total RNA extracted from the dorsal medial prefrontal cortex (dmPFC) was sequenced using the whole transcriptome sequencing protocol. We found 783 genes that were differentially expressed between control and post-dependent rats, including several genes coding epigenetic enzymes. We chose to investigate the effect of reducing expression of one of these enzymes – the histone lysine 9 methyltransferase PRDM2. Thus, a shRNA lentivirus specific to prdm2 was injected into the dmPFC of naïve rats, and tests for alcohol consumption, aversion resistant alcohol seeking, and stress induced reinstatement were performed. Our results demonstrate that inhibition of PRDM2 within the dmPFC is associated with increased alcohol self-administration, a resistance to quinine adulteration, and reinstatement of self-administration at lower shock intensity, suggesting a role for this enzyme in addictive behaviors.

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