Research Service, VA North Texas Health Care System, Dallas, TX 75126-7167
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111.
eNeuro. 2020 Nov 5;7(6). doi: 10.1523/ENEURO.0283-20.2020. Print 2020 Nov/Dec.
Drug addiction and withdrawal are characterized by sleep disruption, but the effects of sleep disruption on these states are not well characterized. Sleep deprivation (SD) immediately before the cocaine conditioning trials enhanced cocaine conditioned place preference (CPP) in a dose-dependent manner (3, 8 mg/kg but not 15 mg/kg) in mice. SD immediately before the postconditioning test also enhanced cocaine CPP preference in a dose-dependent manner (8 mg/kg, but not 3, 15 mg/kg). Exposure to orexin-receptor antagonism (1 mg/kg SB 334867, an orexin 1 receptor antagonist; OX1R) just before cocaine-conditioning trials or the postconditioning test attenuated SD-enhanced preference. This suggests a potential therapeutic role for the manipulation of the orexin system to mitigate drug seeking, especially in the context of sleep loss before drug exposure.
药物成瘾和戒断的特征是睡眠紊乱，但睡眠紊乱对这些状态的影响还没有很好地描述。在可卡因条件作用试验之前立即进行睡眠剥夺（SD），以剂量依赖性的方式增强了可卡因条件性位置偏好（CPP）（3、8mg/kg，但 15mg/kg 没有）。在条件作用后测试之前立即进行 SD 也以剂量依赖性的方式增强了可卡因 CPP 偏好（8mg/kg，但 3、15mg/kg 没有）。在可卡因条件作用试验或条件作用后测试之前，仅仅暴露于食欲素受体拮抗剂（1mg/kg SB 334867，一种食欲素 1 受体拮抗剂；OX1R），可以减弱 SD 增强的偏好。这表明操纵食欲素系统对于减轻药物寻求具有潜在的治疗作用，特别是在暴露于药物之前睡眠不足的情况下。
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