Disruption of the activity-rest cycle by MAOI treatment: dependence on light and a secondary visual pathway to the circadian pacemaker.
The disruptive effects on the activity-rest cycle of the monoamine oxidase inhibitor (MAOI) clorgyline and of continuous light were examined in Syrian hamsters. When administered in dim and moderate light intensities, clorgyline delayed the daily onset of wheel-running. When administered in bright light, it dissociated the circadian rhythm of wheel-running. This dissociation was prevented by lesions of the intergeniculate leaflet of the ventral lateral geniculate nucleus. Constant darkness restored the circadian rhythm of wheel-running in hamsters with disrupted circadian rhythms. The phase of the restored rhythm of wheel-running was shifted 6-12 h later than the phase of wheel-running prior to dissociation. Our results suggest that MAOI treatment weakens the coupling between oscillators that comprise the circadian pacemaker, and augments the disruptive effects of continuous light acting via the intergeniculate leaflet region of the ventral lateral geniculate nucleus. These effects on the circadian pacemaker may be responsible for disruptions of the sleep-wake cycle that occur as side effects when MAOIs are used clinically to treat depression and might play a role in the induction of mania and rapid cycling by antidepressants.
Duncan
W C
WC
Clinical Psychobiology Branch, National Institute of Mental Health, Bethesda, MD 20892, USA. wduncan@box-w.nih.gov
Johnson
K A
KA
Sutin
E
E
Wehr
T A
TA
D000704:Analysis of Variance; D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D003010:Clorgyline / Q000494:pharmacology*; D006224:Cricetinae; D003624:Darkness; D005829:Geniculate Bodies / Q000502:physiology*; D008027:Light; D008029:Lighting; D008297:Male; D008647:Mesocricetus; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D012146:Rest; D014795:Visual Pathways / Q000187:drug effects / Q000502:physiology*
D008996:Monoamine Oxidase Inhibitors; D003010:Clorgyline