Chronobiotic effects of gepirone, a potential antidepressant with 5HT1A receptor partial agonist properties

Abnormal timing in the circadian system is reported in endogenous depression. Gepirone, a 5HT1A 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 hypothesized 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.