Content area
Full Text
COM M U N I T Y CO R N E R
Exploring the epigenetics of cocaine resistance
Michael K Skinner
Drug addiction is known to have a heritable component and to run in families. However, a recent study in rats by Vassoler et al.1 shows an unexpected resultthat the sons of males who had self-administered cocaine had a reduced propensity to take this drug and a delay in their acquisition of drug-seeking behavior. The authors linked these behavioral changes to epigenetic changes in the sperm from cocaine-exposed males and in the brains of their male offspring. We asked four experts to comment on the results of this study and their implications for understanding how addictive phenotypes are inherited.
The recent report by Vassoler et al.1 provides the provocative observation in rats that a fathers ingestion of cocaine can alter the epigenetic programming of his sperm, which then allows the epigenetic inheritance of cocaine resistance in male but not female offspring. Epigenetic alterations in the Bdnf promoter were identified in fathers spermand in brains of male offspring. This is a good example of epigenetic inheritance through alterations in the sperm due to direct exposures to an environmental factor.
Direct exposure to environmental factors has been shown to promote epigenetic alterations in sperm that can influence disease and phenotypes in subsequent generations6. As the germline is directly exposed to the environmental factor to alter epigenetic programming, this information can be transmitted to the F1 offspring. Generally, epigenetic marks get erased and reset after fertilization and embryonic development7, but some epigenetic marks such as DNA methylation can become permanently programmed to promote the epigenetic inheritance of phenotypes8. In the current study, because the F0 father is directly exposed to cocaine, as are the sperm that will generate the F1 offspring, this does not constitute an epigenetic transgenerational inheritance phenotype (which would require transmission to the F2 generation grandchild). A crucial future study will be to determine the potential
Bruce T Hope
npg 2013 Nature America, Inc. All rights reserved.
Cocaine self-administration induces hyperacetylation of the Bdnf promoter and increases expression of brain-derived neurotrophic factor (BDNF) protein in the reward pathway from the ventral tegmental area (VTA) to the nucleus accumbens and the medial prefrontal cortex (mPFC) of...