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.
