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Epigenetic Inheritance of a Cocaine-Resistance Phenotype

Epigenetic Inheritance of a Cocaine-Resistance Phenotype

Fair M Vassoler, Samantha L White, Heath D Schmidt, Ghazaleh Sadri-Vakili, R Christopher Pierce

Nat Neurosci. 2013 Jan;16(1):42-7.

PMID: 23242310

Abstract:

We delineated a heritable phenotype resulting from the self-administration of cocaine in rats. We observed delayed acquisition and reduced maintenance of cocaine self-administration in male, but not female, offspring of sires that self-administered cocaine. Brain-derived neurotrophic factor (Bdnf) mRNA and BDNF protein were increased in the medial prefrontal cortex (mPFC), and there was an increased association of acetylated histone H3 with Bdnf promoters in only the male offspring of cocaine-experienced sires. Administration of a BDNF receptor antagonist (the TrkB receptor antagonist ANA-12) reversed the diminished cocaine self-administration in male cocaine-sired rats. In addition, the association of acetylated histone H3 with Bdnf promoters was increased in the sperm of sires that self-administered cocaine. Collectively, these findings indicate that voluntary paternal ingestion of cocaine results in epigenetic reprogramming of the germline, having profound effects on mPFC gene expression and resistance to cocaine reinforcement in male offspring.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP219766253	ANA-12		219766-25-3	Price

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