Penev P D, Zee P C, Turek F W
National Science Foundation Center for Biological Timing, Northerwestern University, Evanston, IL 60208.
Brain Res. 1994 Feb 21;637(1-2):255-61. doi: 10.1016/0006-8993(94)91241-6.
Injections with the short-acting benzodiazepine, triazolam (Tz), 6 h before activity onset (CT6) produce large phase advances of the circadian pacemaker in hamsters. An increase in locomotor activity and/or the state of arousal is considered essential for the effects of Tz, suggesting the potential involvement of central monoaminergic systems in this process. The present study examines the effect of reserpine-induced monoamine depletion on the phase-shifting effects of Tz in hamsters. Wheel running activity of 16 male golden hamsters (14 weeks old) was continuously monitored in constant darkness. After a stable free-running circadian rhythm was established half of the animals received reserpine (2.5 mg/kg, s.c.) and the other half vehicle treatment. Ten days later all animals were given Tz injections (10 mg/kg i.p.) at CT6 and the circadian activity rhythm was monitored for 2 more weeks. An additional 10 animals were used to determine the effect of reserpine on the central monamine levels using high pressure liquid chromatography. A circadian rhythm of locomotor activity with reduced amplitude and longer free-running period persisted after reserpine treatment, despite the significant monoamine depletion. Triazolam injections at CT6 induced large phase-advances (93.1 +/- 14.9) in the control group that were markedly attenuated in 7 out of the 8 reserpine-treated animals (3.12 +/- 17.7 min, P < 0.01). Our results suggest that monoaminergic systems are essential for the phase-shifting effect of Tz upon the circadian system in hamsters.
在活动开始前6小时（CT6）注射短效苯二氮䓬类药物三唑仑（Tz），可使仓鼠的昼夜节律起搏器产生大幅度的相位提前。运动活动和/或觉醒状态的增加被认为是Tz产生作用的必要条件，这表明中枢单胺能系统可能参与了这一过程。本研究考察了利血平诱导的单胺耗竭对Tz在仓鼠中相移作用的影响。在持续黑暗中连续监测16只雄性金黄仓鼠（14周龄）的转轮活动。在建立稳定的自由运行昼夜节律后，一半动物接受利血平（2.5mg/kg，皮下注射），另一半接受赋形剂处理。10天后，所有动物在CT6时接受Tz注射（10mg/kg，腹腔注射），并再监测2周的昼夜活动节律。另外使用10只动物通过高压液相色谱法测定利血平对中枢单胺水平的影响。尽管单胺显著耗竭，但利血平处理后仍维持了运动活动的昼夜节律，但其振幅降低且自由运行周期延长。在CT6注射三唑仑在对照组中诱导了大幅度的相位提前（93.1±14.9），在8只接受利血平处理的动物中有7只明显减弱（3.12±17.7分钟，P<0.01）。我们的结果表明，单胺能系统对于Tz对仓鼠昼夜节律系统的相移作用至关重要。
