Liability to develop drug addiction is heritable, but the precise contribution of non-Mendelian factors is not well understood. Here we separate male rats into addiction-like and non-addiction-like groups, based on their incentive motivation to seek cocaine. We find that the high incentive responding of the F0 generation could be transmitted to F1 and F2 generations. Moreover, the inheritance of high incentive response to cocaine is contingent on high motivation, as it is elicited by voluntary cocaine administration, but not high intake of cocaine itself. We also find DNA methylation differences between sperm of addiction-like and non-addiction-like groups that were maintained from F0 to F1, providing an epigenetic link to transcriptomic changes of addiction-related signalling pathways in the nucleus accumbens of offspring. Our data suggest that highly motivated drug seeking experience may increase vulnerability and/or reduce resistance to drug addiction in descendants.
See Huang and Gitler (doi:) for a scientific commentary on this article.Small molecule drugs that can reduce levels of the mutant huntingtin protein (mHTT) are sought for the treatment of Huntington’s disease. Song et al. demonstrate that deleting Gpr52, or inhibiting Gpr52 protein function with a novel small molecule antagonist, reduces mHTT levels and rescues Huntington’s disease-associated phenotypes in cellular and mouse models.
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