Van Reeth O, Vanderhaeghen J J, Turek F W
Laboratory of Neuropathology and Neuropeptides Research, Free University of Brussels, Belgium.
Brain Res. 1988 Mar 22;444(2):333-9. doi: 10.1016/0006-8993(88)90942-0.
A single injection of the short acting benzodiazepine, triazolam, can induce permanent phase advances as well as phase delays in the onset of the circadian rhythm of wheel running behavior in hamsters free-running under constant environmental conditions. If the phase shifting effects of triazolam on the circadian system are mediated through the benzodiazepine-GABA receptor complex, then it should be possible to block these effects with RO 15-1788, a selective benzodiazepine antagonist, which acts at the benzodiazepine-GABA receptor level. To test this hypothesis, hamsters free running in constant light received an intraperitoneal injection of various doses of Ro 15-1788 15 min before a single i.p. injection of 0.5 mg of triazolam. This dose of triazolam is known to induce maximal phase shifts in the circadian rhythm of wheel running behavior in hamster. Treatment with Ro 15-1788 totally blocked both the phase advancing and phase delaying effects of triazolam, while the administration of Ro 15-1788 alone did not phase shift the activity rhythm. These results support the hypothesis that the phase shifting effects of triazolam are mediated through the benzodiazepine-GABA receptor complex. The absence of any phase shifting effects of Ro 15-1788 when delivered alone suggests that Ro 15-1788 has no partial agonist properties in this experimental paradigm.
单次注射短效苯二氮䓬类药物三唑仑，可使处于持续环境条件下自由活动的仓鼠的昼夜节律中轮子转动行为的开始时间出现永久性的相位提前以及相位延迟。如果三唑仑对昼夜节律系统的相位移动效应是通过苯二氮䓬 - GABA受体复合物介导的，那么应该可以用RO 15 - 1788（一种选择性苯二氮䓬拮抗剂，作用于苯二氮䓬 - GABA受体水平）来阻断这些效应。为了验证这一假设，在持续光照下自由活动的仓鼠在单次腹腔注射0.5毫克三唑仑前15分钟接受了不同剂量的RO 15 - 1788腹腔注射。已知该剂量的三唑仑能在仓鼠轮子转动行为的昼夜节律中诱导最大相位移动。用RO 15 - 1788治疗完全阻断了三唑仑的相位提前和相位延迟效应，而单独给予RO 15 - 1788并未使活动节律发生相位移动。这些结果支持了三唑仑的相位移动效应是通过苯二氮䓬 - GABA受体复合物介导的这一假设。单独给予RO 15 - 1788时未出现任何相位移动效应，这表明在该实验范式中RO 15 - 1788没有部分激动剂特性。
