A serotonin neurotoxin attenuates the phase-shifting effects of triazolam on the circadian clock in hamsters

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Several lines of evidence suggest the potential involvement of serotonergic pathways in mediating the effects of activity-inducing stimuli on the circadian clock in rodents. The aim of the present 3 experiments was to examine the effects of the serotonergic neurotoxin, p-hloroamphetamine (PCA, 10 mg/kg) on: (1) the monoamine levels of the hypothalamus, frontal cortex and hippocampus in the hamster; (2) the phase shifts in the circadian rhythm of locomotor activity of hamsters in response to treatment with the short-acting benzodiazepine, triazolam (7.5 mg/kg); and (3) the magnitude of the acute increase in locomotor activity associated with triazolam administration in this species. The administration of PCA to hamsters caused changes of specific monoaminergic systems in the hypothalamus, that were limited to a selective decrease in serotonin levels 7 days post-treatment. The phase shifts of the circadian clock in response to triazolam treatment at CT 6 were considerably attenuated following the administration of the 5-HT neurotoxin. The total amount and the profiles of triazolam-induced wheel-running and general cage activity between CT 6 and CT 12 were not significantly affected by the PCA treatment. The finding that a 5-HT neurotoxin can attenuate the phase-shifting effects of triazolam in hamsters, without interfering with its activity-inducing properties, suggests that serotonergic afferents might be involved in the mechanism for non-photic phase-shifting of the circadian system.

Original languageEnglish (US)
Pages (from-to)207-216
Number of pages10
JournalBrain research
Volume669
Issue number2
DOIs
StatePublished - Jan 16 1995

Funding

We wish to thank Dr. J. Levine for the use of the HPLC equipment. This work was supported by the NSF Science and Technology Center for Biological Timing, NIH Grants AG-09297, AG-10870 and a NIH Center Core Grant P-30 HD-28048.

Keywords

  • Benzodiazepine
  • Circadian rhythm
  • Locomotor activity
  • Monoamine
  • p-Chloroamphetamine

ASJC Scopus subject areas

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

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