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.
Duncan
W C
WC
Section on Biological Rhythms, National Institute of Mental Health, NIH, Bethesda, MD 20892, USA. wduncan@box-w.nih.gov
Johnson
K A
KA
Wehr
T A
TA
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002940:Circadian Rhythm / Q000187:drug effects*; D003010:Clorgyline / Q000494:pharmacology*; D006224:Cricetinae; D008647:Mesocricetus; D009043:Motor Activity / Q000187:drug effects; D011985:Receptors, Serotonin / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013493:Suprachiasmatic Nucleus / Q000737:chemistry / Q000187:drug effects / Q000502:physiology