Sa. Ferguson et al., Nicotine phase shifts the 6-sulphatoxymelatonin rhythm and induces c-Fos in the SCN of rats, BRAIN RES B, 48(5), 1999, pp. 527-538
The neurotransmitter acetylcholine is not found in the major suprachiasmati
c nuclei afferents reported to mediate light effects on entrainment and pha
se shifts in mammals; however it clearly has some role in the control of ci
rcadian rhythmicity, This study examined the effect of the cholinergic agon
ists nicotine and oxotremorine on (1) the rhythmic production of melatonin
using the metabolite, 6-sulphatoxymelatonin as a marker, and (2) the expres
sion of c-Fos protein in the suprachiasmatic nuclei (SCN) of the rat. Nicot
ine administration (1 mg/kg, s.c.) caused phase delays in the timing of the
onset of 6-sulphatoxymelatonin excretion (compared to the pre-treatment ni
ght), when administered at circadian time (CT)16 (1.7 +/- 0.3 h delay) and
CT18 (1.7 +/- 0.2 h delay) but not at CT14 (0.8 +/- 0.3 h delay), whereas o
xotremorine and saline administration had no effect on the timing of the me
latonin rhythm. Nicotine administration also caused the induction of c-fos-
like immunoreactivity in the SCN in a dose- and time-dependent manner, Furt
her, pre-treatment with the nicotinic antagonist mecamylamine reduced the n
umber of nicotine-induced c-Fos-positive cells in the SCN by 65%, These dat
a indicate that cholinergic neurons may alter the timing of the onset of me
latonin excretion by a direct or indirect effect on the SCN possibly mediat
ed by the nicotinic receptor. (C) 1999 Elsevier Science Inc.