Sex differences in prenatal stress effects on cocaine pursuit in rats.
Sex differences in prenatal stress effects on cocaine pursuit in rats.
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DOI：
10.1016/j.physbeh.2017.10.019
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发表时间：
2019-05-01
影响因子：
2.9
通讯作者：
Becker JB
中科院分区：
文献类型：
--
作者：
Thomas MB;Becker JB
早期生命个体发育的中断对发育中的有机体的健康具有严重和持久的后果。临床和临床前研究结果均表明，这种干扰可由孕期母体应激(产前应激[PS])引起。在大鼠身上，PS促进了药物的奖赏和神经化学刺激作用，这表明PS可能是人类滥用药物的一个危险因素。然而，它对女性的影响知之甚少，尽管在没有PS(NPS)对照的情况下，药物敏感性的性别差异已经被很好地记录下来。因此，我们用延长的药物自我给药方案测试了怀孕最后一周的母亲束缚压力和性别对药物使用的独立影响和交互作用。雄性和雌性大鼠在七周内每天都可以接触到大量但受控制的可卡因。最后一周的药物追逐被用来指示对发展成瘾样表型的易感性，这是基于报告称，经过几周的测试后，药物使用变得越来越强迫性。总体而言，雌性比雄性更符合成瘾标准，与NPS对照组相比，PS大鼠也是如此。此外，性和PS的交互作用不成比例地促进了有PS病史的女性的药物追求。这些结果表明，药物敏感性的性别差异随着持续的药物暴露而持续存在，PS通过更严重地影响女性来扩大这种差异。总而言之，PS可能是人类吸毒成瘾的危险因素，在更大程度上是女性对男性的依赖。
Disruption of early-life ontogeny has severe and persistent consequences for the health of the developing organism. Both clinical and preclinical findings indicate that such interference can be caused by maternal stress during the gestation period (prenatal stress [PS]). In rats, PS facilitates the rewarding and neurochemical-stimulating effects of drugs, suggesting that PS may represent a risk factor for drug abuse in humans. Very little, however, is known about its effects in females, even though sex differences in drug susceptibility have been well documented in no PS (NPS) controls. Thus, we tested for independent effects and interactions between maternal restraint stress during the last week of gestation and sex on drug use with an extended regimen of drug self-administration. Male and female rats were provided daily access to a large but controlled amount of cocaine for seven weeks. Drug pursuit during the final week was used to indicate susceptibility to developing an addiction-like phenotype, based on reports that drug use becomes increasingly compulsive-like after weeks of testing. Overall, females satisfied more addiction-like criteria than males, and the same was true for PS rats when compared to NPS controls. In addition, sex and PS interacted to disproportionately promote drug pursuit of females with a history of PS. These results indicate that sex differences in drug susceptibility persist with continued drug exposure, and that PS widens this difference by more severely affecting females. In all, PS may be a risk factor for drug addiction in humans, and to a greater extent in women vs. men.
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