Drug-seeking motivation level in male rats determines offspring susceptibility or resistance to cocaine-seeking behaviour.
Drug-seeking motivation level in male rats determines offspring susceptibility or resistance to cocaine-seeking behaviour.
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DOI：
10.1038/ncomms15527
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发表时间：
2017-05-30
影响因子：
16.6
通讯作者：
Ma L
中科院分区：
文献类型：
--
作者：
Le Q;Yan B;Yu X;Li Y;Song H;Zhu H;Hou W;Ma D;Wu F;Zhou Y;Ma L
易患药物成瘾是遗传的，但非孟德尔因素的确切贡献还不清楚。在这里，我们将雄性大鼠分为成瘾和非成瘾组，基于他们寻求可卡因的动机。结果表明，F0代的高激励反应可以传递到F1和F2代。此外，对可卡因的高刺激反应的遗传取决于高动机，因为它是由自愿服用可卡因引起的，而不是可卡因本身的高摄入量。我们还发现，从F0到F1维持的成瘾样和非成瘾样组的精子之间的DNA甲基化差异，为后代的核内成瘾相关信号通路的转录组学变化提供了表观遗传学联系。我们的数据表明，高度积极的药物寻求的经验可能会增加脆弱性和/或减少后代对药物成瘾的抵抗力。药物成瘾是部分遗传的，但非遗传遗传机制还没有很好地理解。作者表明，雄性大鼠对可卡因自我给药的反应动机引起后代对成瘾样行为的易感性和/或抵抗力降低。
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. Drug addiction is partially heritable but the non-genetic inheritance mechanisms are not well understood. The authors show that motivation of male rats in response to cocaine self-administration elicit susceptibility and/or decreased resistance to developing addiction like behaviour in offspring.