Phase-resetting response to (+)8-OH-DPAT, a serotonin 1A/7 receptor agonist, in the mouse in vivo

Several lines of evidence indicate that 5-HT neuronal systems may play a critical role for the non-photic entrainment of the rodent circadian clock. Although it is well established that (+)8-hydroxy-2-(di-n-propylamino)tetralin [(+)8-OH-DPAT], a 5-HT _1A/7 receptor agonist, causes a phase-advance of behavioral rhythm in hamsters, little is known whether this agent produces phase shifts of activity rhythm in mice. Therefore, we examined the effect of (+)8-OH-DPAT on the mouse locomotor activity rhythm. Systemic administration of this chemical at mid-subjective daytime induced a clear and dose-dependent phase advance, while there were no significant phase shifts at other times (early-subjective day, late-subjective day, or subjective night). Additionally, (+)8-OH-DPAT accelerated the re-entrainment of mouse behavioral rhythm to a 6-h advanced light-dark cycle. These results suggest that we can use mice for understanding the molecular mechanism of (+)8-OH-DPAT-induced phase shift because of availability of clock gene targeted mice.