Chronobiotic effects of gepirone, a potential antidepressant with 5HT(1A) receptor partial agonist properties

Oliver Van Reeth*, E. Olivares, Y. Zhang, B. Tripathi, Fred W Turek

*Corresponding author for this work

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Abnormal timing in the circadian system is reported in endogenous depression. Gepirone, a 5HT(1A) receptor partial agonist, has anxiolytic and antidepressant properties. We determined whether gepirone was able to modify the functioning of the circadian system. Single i.p. injections of gepirone in hamsters induced phase-advances in the circadian activity rhythm when administered during the subjective day, but had no effect when given during the subjective night. Single i.p. gepirone injections also blocked the phase-shifting effects of a light pulse, at a time when gepirone by itself had no effect on the activity rhythm. Chronic gepirone treatment in hamsters kept under a 14/10 light-dark cycle induced a phase-advance in the activity rhythm, modifying the phase-relationship between this rhythm and the light-dark cycle. After transfer to constant darkness, gepirone-treated hamsters showed a shortened free-running period of activity, compared to controls. Both acute and chronic gepirone treatment thus have major effects on the circadian rhythm of locomotor activity in rodents. In view of the hypothetized role for disturbed circadian rhythms in the pathophysiology of depression, and the use of 5HT-related drugs for its treatment, the results provide further support for the possibility that some of the therapeutic effects of these compounds may be due to their effects on temporal organization.

Original languageEnglish (US)
Pages (from-to)119-130
Number of pages12
JournalBehavioural Pharmacology
Volume10
Issue number2
DOIs
StatePublished - Jan 1 1999

Keywords

  • Circadian clock
  • Depression
  • Gepirone
  • Hamster
  • Light
  • Phase
  • Rhythms
  • Serotonin

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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