A cholinergic antagonist, mecamylamine, blocks light-induced fos immunoreactivity in specific regions of the hamster suprachiasmatic nucleus.
Recent studies have shown that light-induced phase shifts of the circadian rhythm of locomotor activity are associated with c-fos expression in the suprachiasmatic nucleus (SCN) of rodents. In order to explore further the importance of c-fos expression for the phase-shifting effects of light, we examined the effects of mecamylamine on light-induced Fos-like immunoreactivity (Fos-lir) in the SCN. Mecamylamine was chosen because it is a cholinergic antagonist that blocks the phase-shifting effects of light on the circadian activity rhythm in the golden hamster. Golden hamsters were entrained for at least 14 days to a 14 h light: 10 h dark photoperiod. Animals were then placed in constant darkness (DD) and during exposure to DD were subjected to one or more of the following treatments: (1) vehicle alone; (2) mecamylamine alone (450 micrograms, i.c.v.) at circadian time (CT) 19; (3) vehicle plus a light pulse at CT 19; (4) mecamylamine 10 min prior to the light pulse at CT 19. Mecamylamine blocked the phase-shifting effects of light on the circadian rhythm of locomotor activity when compared to vehicle-treated animals (P < 0.001). A light pulse at CT 19 induced Fos-lir in the SCN within 1 h, whereas treatment with vehicle or mecamylamine had no noticeable effect on Fos-lir in the SCN. Mecamylamine pretreatment dramatically reduced light-induced Fos-lir in the SCN by 75%. The most striking observation was the clear inhibition of Fos-lir by mecamylamine in the dorsomedial region of the SCN while there was little inhibition of Fos-lir in the most ventral portions of the SCN.(ABSTRACT TRUNCATED AT 250 WORDS)
Zhang
Y
Y
NSF Center for Biological Timing, Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208.
Zee
P C
PC
Kirby
J D
JD
Takahashi
J S
JS
Turek
F W
FW
D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects; D006224:Cricetinae; D008027:Light; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology*; D008647:Mesocricetus; D009043:Motor Activity / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000276:immunology; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects
D010276:Parasympatholytics; D016760:Proto-Oncogene Proteins c-fos; D008464:Mecamylamine