5-HT agonist-induced phase-advances of the circadian pacemaker are diminished by chronic antidepressant drug treatment.

Serotonin (5-HT) and its agonists alter the timing of the circadian pacemaker. Previous research has shown that when they are injected 4 h before or after the onset of wheel-running, they phase-advance or delay, respectively, the timing of the pacemaker. Because serotonergic interventions alter 5-HT receptor number in the hypothalamus, we asked whether chronic treatment with an antidepressant drug (AD) that modifies serotonergic function could alter the phase-shifting effects of the 5-HT agonist 8-hydroxydipropylaminotetralin (8-OH-DPAT). Hamsters were treated chronically with the monoamine oxidase inhibitor (MAOI), clorgyline, and then injected with 8-OH-DPAT or vehicle (VEH) either 4 h before or after the onset of wheel-running. MAOI treatment decreased the magnitude of both 8-OH-DPAT- and VEH-induced phase advances, but not the magnitude of 8-OH-DPAT-induced phase-delays. The results indicate that 8-OH-DPAT-induced phase-advances and delays are functionally distinct with regard to adaptive changes during chronic AD treatment.