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

Abstract

The neurotransmitter acetylcholine is not found in the major suprachiasmatic nuclei afferents reported to mediate light effects on entrainment and phase shifts in mammals; however it clearly has some role in the control of circadian rhythmicity. This study examined the effect of the cholinergic agonists nicotine and oxotremorine on (1) the rhythmic production of melatonin using the metabolite, 6-sulphatoxymelatonin as a marker, and (2) the expression of c-Fos protein in the suprachiasmatic nuclei (SCN) of the rat. Nicotine administration (1 mg/kg, s.c.) caused phase delays in the timing of the onset of 6-sulphatoxymelatonin excretion (compared to the pre-treatment night), 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 oxotremorine and saline administration had no effect on the timing of the melatonin rhythm. Nicotine administration also caused the induction of c-Fos-like immunoreactivity in the SCN in a dose- and time-dependent manner. Further, pre-treatment with the nicotinic antagonist mecamylamine reduced the number of nicotine-induced c-Fos-positive cells in the SCN by 65%. These data indicate that cholinergic neurons may alter the timing of the onset of melatonin excretion by a direct or indirect effect on the SCN possibly mediated by the nicotinic receptor.