期刊
NATURE NEUROSCIENCE
卷 16, 期 1, 页码 42-U67出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.3280
关键词
-
资金
- US National Institutes of Health [R01s DA15214, DA22339, DA33641, K02 DA18678, K01 DA30445, F31 DA31535, T32s DA28874, MH86599]
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM007517] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH086599, R56MH086599] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [T32DA028874, K02DA018678, R01DA015214, F31DA031535, R01DA033641, R01DA022339, K01DA030445] Funding Source: NIH RePORTER
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据