Akbarabadi Ardeshir, Niknamfar Saba, Vousooghi Nasim, Sadat-Shirazi Mitra-Sadat, Toolee Heidar, Zarrindast Mohammad-Reza
Genetics Laboratory, Iranian National Center for Addiction Studies (INCAS), Tehran University of Medical Sciences, Tehran, Iran.
Biology department, Faculty of Biological Sciences, Islamic Azad University, North Tehran Branch, Tehran, Iran.
Physiol Behav. 2018 Feb 1;184:143-149. doi: 10.1016/j.physbeh.2017.11.024. Epub 2017 Nov 23.
Drug addiction is a chronic disorder resulted from complex interaction of genetic, environmental, and developmental factors. Epigenetic mechanisms play an important role in the development and maintenance of addiction and also memory formation in the brain. We have examined passive avoidance memory and morphine conditioned place preference (CPP) in the offspring of male and/or female rats with a history of adulthood morphine consumption. Adult male and female animals received chronic oral morphine for 21days and then were maintained drug free for 10days. After that, they were let to mate with either an abstinent or control rat. Male offspring's memory was evaluated by step through test. Besides, rewarding effects of morphine were checked with CCP paradigm. Offspring of abstinent animals showed significant memory impairment compared to the control group which was more prominent in the offspring of abstinent females. Conditioning results showed that administration of a high dose of morphine (10mg/kg) that could significantly induce CPP in control rats, was not able to induce similar results in the offspring of morphine abstinent parents; and CPP was much more prominent when it was induced in the offspring of morphine exposed females compared to the progeny of morphine exposed males. It is concluded that parental morphine consumption in adulthood even before mating has destructive effects on memory state of the male offspring and also leads to tolerance to the rewarding effects of morphine. These effects are greater when the morphine consumer parent is the female one.
药物成瘾是一种由遗传、环境和发育因素复杂相互作用导致的慢性疾病。表观遗传机制在成瘾的发展和维持以及大脑中的记忆形成中起着重要作用。我们研究了成年期有吗啡使用史的雄性和/或雌性大鼠后代的被动回避记忆和吗啡条件性位置偏爱(CPP)。成年雄性和雌性动物接受为期21天的慢性口服吗啡治疗,然后停药10天。之后,让它们与戒断或对照大鼠交配。通过穿梭箱试验评估雄性后代的记忆。此外,用CPP范式检查吗啡的奖赏效应。与对照组相比,戒断动物的后代表现出明显的记忆损伤,这在戒断雌性后代中更为突出。条件性试验结果表明,高剂量吗啡(10mg/kg)在对照大鼠中可显著诱导CPP,但在吗啡戒断亲本的后代中不能诱导出类似结果;与吗啡暴露雄性后代相比,在吗啡暴露雌性后代中诱导CPP时更为明显。结论是,成年期甚至在交配前的亲本吗啡使用对雄性后代的记忆状态有破坏性影响,并且还导致对吗啡奖赏效应的耐受性。当使用吗啡的亲本为雌性时,这些影响更大。