Nicotine phase shifts the 6-sulphatoxymelatonin rhythm and induces c-Fos in the SCN of rats

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.