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Drug-seeking motivation level in male rats determines offspring susceptibility or resistance to cocaine-seeking behaviour

机译:雄性大鼠的药物寻找动机水平决定了后代对可卡因寻找行为的敏感性或耐药性

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摘要

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.
机译:发展成瘾的责任是可遗传的,但是对非孟德尔因素的确切贡献尚不清楚。在这里,我们根据雄性大鼠寻找可卡因的动机将其分为成瘾型和非成瘾型组。我们发现,F0代的高激励响应可以传递给F1和F2代。此外,对可卡因的高刺激性反应的遗传取决于高刺激性,因为这是由自愿性可卡因管理引起的,但不是高摄入可卡因本身。我们还发现从F0到F1维持成瘾样和非成瘾样组的精子之间的DNA甲基化差异,为后代伏核中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,积极进取的吸毒经历可能会增加后代的脆弱性和/或降低其对药物成瘾的抵抗力。

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