MONOAMINE DEPLETION BLOCKS TRIAZOLAM-INDUCED PHASE ADVANCES OF THE CIRCADIAN CLOCK IN HAMSTERS

Injections with the short-acting benzodiazepine, triazolam (Tz), 6 h b efore activity onset (CT6) produce large phase advances of the circadi an pacemaker in hamsters. An increase in locomotor activity and/or the state of arousal is considered essential for the effects of Tz, sugge sting the potential involvement of central monoaminergic systems in th is 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 c ontinuously monitored in constant darkness. After a stable free-runnin g circadian rhythm was established half of the animals received reserp ine (2.5 mg/kg, s.c.) and the other half vehicle treatment. Ten days l ater 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 addit ional 10 animals were used to determine the effect of reserpine on the central monoamine levels using high pressure liquid chromatography. A circadian rhythm of locomotor activity with reduced amplitude and lon ger free-running period persisted after reserpine treatment, despite t he significant monoamine depletion. Triazolam injections at CT6 induce d 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.