Van Reeth O, Tripathi B, Kirby J, Laartz B, Tecco J, Turek F W
Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208.
Proc Soc Exp Biol Med. 1994 Jun;206(2):138-44. doi: 10.3181/00379727-206-43732.
The ability of mammals to measure seasonal changes in daylength depends upon a circadian clock and the phase-relationship between this clock and the light: dark cycle. Recently, a number of pharmacological and nonpharmacological stimuli have been shown to have pronounced effects on the phase of the circadian clock of rodents. The objective of the present study was to determine if a drug-induced change in the phase-relationship between a measurable circadian rhythm (i.e., wheel running behavior) and the light:dark cycle would alter the effects of the light cycle on the neuroendocrine-gonadal axis. Adult male hamsters with regressed testes due to exposure to an inhibitory 10:14-hr light:dark cycle were daily injected with vehicle or the short-acting benzodiazepine, triazolam, while remaining on short days, while a control group of hamsters was transferred to a photostimulatory 14:10-hr light:dark cycle. Two other groups of hamsters with regressed testes were blinded and daily injected with vehicle or triazolam. The injections were timed to occur about 4 hr before activity onset because previous studies had demonstrated that injections of triazolam at this time can lead to a phase advance in the activity rhythm. The circadian rhythm of wheel running behavior was measured in all the animals maintained on the 10:14-hr light:dark cycle in order to monitor circadian phase. While no testicular growth was observed after 25 days of vehicle injections, growth was observed in the triazolam-treated animals that was comparable to that observed in control animals transferred to long days. Testicular growth in triazolam-treated animals was associated with an earlier onset of locomotor activity, when compared with the vehicle-treated animals. Importantly, triazolam had no effect on the testicular size of blind animals. These results indicate that daily injections of triazolam can stimulate neuroendocrine-gonadal activity by altering the phase-relationship between the cycle and the circadian clock involved in photoperiodic time measurement, and that agents which can affect the clock may be useful in altering seasonal cycles.
哺乳动物测量白昼长度季节性变化的能力取决于昼夜节律钟以及该时钟与光暗周期之间的相位关系。最近,一些药理学和非药理学刺激已被证明对啮齿动物昼夜节律钟的相位有显著影响。本研究的目的是确定药物诱导的可测量昼夜节律(即轮转行为)与光暗周期之间相位关系的变化是否会改变光周期对神经内分泌-性腺轴的影响。因暴露于抑制性的10:14小时光暗周期而睾丸萎缩的成年雄性仓鼠,在短日照条件下每天注射赋形剂或短效苯二氮䓬类药物三唑仑,而另一组对照组仓鼠则转移到光刺激的14:10小时光暗周期。另外两组睾丸萎缩的仓鼠被致盲,并每天注射赋形剂或三唑仑。注射时间安排在活动开始前约4小时,因为先前的研究表明此时注射三唑仑可导致活动节律提前。对所有维持在10:14小时光暗周期的动物测量轮转行为的昼夜节律,以监测昼夜相位。在注射赋形剂25天后未观察到睾丸生长,但在三唑仑处理的动物中观察到了生长,其生长情况与转移到长日照的对照动物相当。与注射赋形剂的动物相比,三唑仑处理的动物睾丸生长与运动活动的更早开始有关。重要的是,三唑仑对致盲动物的睾丸大小没有影响。这些结果表明,每天注射三唑仑可通过改变光周期与参与光周期时间测量的昼夜节律钟之间的相位关系来刺激神经内分泌-性腺活动,并且能够影响生物钟的药物可能有助于改变季节性周期。