Monoamine depletion blocks triazolam-induced phase advances of the circadian clock in hamsters

Plamen D. Penev*, Phyllis C. Zee, Fred W. Turek

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

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 monoamine 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.

Original languageEnglish (US)
Pages (from-to)255-261
Number of pages7
JournalBrain research
Volume637
Issue number1-2
DOIs
StatePublished - Feb 21 1994

Keywords

  • Aging
  • Arousal
  • Circadian rhythm
  • Locomotor activity

ASJC Scopus subject areas

  • Clinical Neurology
  • Molecular Biology
  • General Neuroscience
  • Developmental Biology

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