Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Brain Res Bull. 2019 Apr;147:124-132. doi: 10.1016/j.brainresbull.2019.02.004. Epub 2019 Feb 12.
The developing brain is extremely sensitive to drugs during adolescence. The devastating impacts of opioid abuse in this critical period not only do involve individuals but also are witnessed in the subsequent generations. Therefore, what is recognized as the population susceptible to the effects of opioid abuse could be much greater in number. In this study, we explored the transgenerational effects of morphine exposure in adolescent stage on morphine reward in male offspring through the patriline. Male Wistar rats underwent 10 days of incremental doses of morphine administration during adolescence; the broad spectrum of neurobehavioral alterations in rat adolescence is akin to that of human adolescence. Thereafter, following a 20-day wash-out period, adult males copulated with naïve females. The adult male offspring were examined for morphine (0, 1, 2 and 5 mg/kg)-induced conditioned place preference (CPP). Moreover, the spontaneous activity of ventral tegmental area (VTA) dopamine (DA) neurons was investigated utilizing extracellular single-unit recording technique. Our results demonstrated that paternal morphine exposure prior to conception leads to the development of a tolerance to the rewarding effects of morphine at the low dose of 1 mg/kg (rightward shift in dose-effect curve). Furthermore, morphine-sired rats elicited a decrease in spontaneous burst firing of VTA DA neurons (burst event frequency, bursting activity and burst duration) compared to saline-sired ones. Hence, our study has provided evidence that paternal morphine exposure during adolescence alters the rewarding effects of morphine in male offspring. This effect may be mediated in part by a decrease in phasic activation of VTA DA neurons.
青春期大脑对药物极为敏感。在这个关键时期，阿片类药物滥用的破坏性影响不仅涉及个人，而且还会在随后的几代人中出现。因此，被认为易受阿片类药物滥用影响的人群数量可能会更多。在这项研究中，我们通过父系探讨了青春期暴露于吗啡对雄性后代吗啡奖赏的跨代影响。雄性 Wistar 大鼠在青春期接受了 10 天递增剂量的吗啡给药；大鼠青春期的广泛神经行为改变类似于人类青春期。此后，经过 20 天的洗脱期，成年雄性与未交配的雌性交配。成年雄性后代接受了吗啡（0、1、2 和 5mg/kg）诱导的条件位置偏好（CPP）检测。此外，还利用细胞外单细胞记录技术研究了腹侧被盖区（VTA）多巴胺（DA）神经元的自发活动。我们的结果表明，在受孕前，父系吗啡暴露会导致对低剂量吗啡（1mg/kg）奖赏效应产生耐受性（剂量-效应曲线右移）。此外，与生理盐水生育的大鼠相比，吗啡生育的大鼠 VTA DA 神经元的自发爆发放电活动减少（爆发事件频率、爆发活动和爆发持续时间）。因此，我们的研究提供了证据，表明青春期父系吗啡暴露会改变雄性后代对吗啡的奖赏效应。这种效应可能部分是通过 VTA DA 神经元的相位激活减少介导的。
