Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Center for Excellence in Brain Science and Intelligence Technology (Institute of Neuroscience), Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, China.
Neurosci Lett. 2023 Sep 25;814:137440. doi: 10.1016/j.neulet.2023.137440. Epub 2023 Aug 14.
Sleep deficiency is known as an important risk factor for relapse to drug abuse, especially for the powerful psychostimulant methamphetamine (METH). On the other hand, both drug addiction and sleep neurobiology are affected by sex hormones. We, therefore, aimed to examine the probable effects of sleep deprivation (SD) on methamphetamine (METH) reward memory in male and female rats. Moreover, we asked if sex hormones influence the effects of SD on METH reward memory. Adult male and female Wistar rats were divided into two main groups, sham and gonadectomized groups. Three weeks later, they were conditioned to receive METH (2 mg/kg, i.p.) in the conditioned place preference. METH reward memory was then reinstated following a 10-day extinction period. SD was induced for 72 h, either before or after extinction, in different groups. In gonadectomized animals, they daily received either subcutaneous administration of estrogen (5 μg/0.1 ml oil) or progesterone (2 mg/0.1 ml oil) or dihydrotestosterone (25 mg/0.1 ml oil) for thirteen days, from post-conditioning day to reinstatement session. We found that SD facilitated relapse to METH reward memory, depending on the time interval between SD and METH reinstatement. Furthermore, we found that estrogen and SD showed synergistic effects to facilitate METH reward memory, whereas testosterone and progesterone revealed inhibitory effects in the controls, but not in the SD, animals. Our findings would seem to suggest that sex hormones should be considered as determinant factors to manage METH abuse and relapse to METH seeking/taking behavior, especially for those with sleep deficiency.
睡眠不足被认为是导致药物滥用复发的一个重要危险因素，尤其是对于强效精神兴奋剂——甲基苯丙胺（METH）。另一方面，药物成瘾和睡眠神经生物学都受到性激素的影响。因此，我们旨在研究睡眠剥夺（SD）对雄性和雌性大鼠 METH 奖励记忆的可能影响。此外，我们还询问了性激素是否会影响 SD 对 METH 奖励记忆的影响。成年雄性和雌性 Wistar 大鼠被分为两个主要组，即假手术组和性腺切除术组。三周后，它们接受条件性位置偏好训练，接受 METH（2 mg/kg，ip）。在 10 天的消退期后，重新激发 METH 奖励记忆。在不同组中，SD 分别在消退前或消退后诱导 72 小时。在性腺切除动物中，它们每天接受皮下注射雌激素（5μg/0.1ml 油）、孕激素（2mg/0.1ml 油）或二氢睾酮（25mg/0.1ml 油），共 13 天，从条件后第一天到再激发期。我们发现，SD 促进了 METH 奖励记忆的复发，这取决于 SD 和 METH 再激发之间的时间间隔。此外，我们发现雌激素和 SD 表现出协同作用，促进 METH 奖励记忆，而睾酮和孕酮在对照组中表现出抑制作用，但在 SD 动物中没有。我们的研究结果表明，性激素应被视为管理 METH 滥用和复发的决定性因素，尤其是对于那些有睡眠不足的人。
