Muscarinic receptors mediate carbachol-induced phase shifts of circadian activity rhythms in Syrian hamsters

Carbachol, a non-specific cholinergic agonist, when administered intraventricularly or directly into the suprachiasmatic nucleus (SCN), causes phase-dependent shifts in circadian rhythms of wheel-running activity in rodents. The cholinergic receptor subtype involved in mediating these carbachol-induced phase shifts, however, remains uncertain. In order to investigate this issue we injected carbachol into the SCN through indwelling cannulas at circadian times (CT) 6, 14 and 22 in Syrian hamsters (Mesocricetus auratus) maintained in constant darkness. Carbachol elicited large phase advances at CT 6 (69.8 ± 15.7 min; mean ±S.E.M.) and CT 22 (83.9 ± 24.8 min) and phase delays at CT 14 (59.7 ± 18 min). We attempted to block the carbachol-induced phase shifts at these three phases using specific antagonists of nicotinic and muscarinic receptors. Mecamylamine, a nicotinic receptor antagonist, did not block carbachol-induced phase shifts at any of the phases tested. Atropine, a muscarinic receptor antagonist, blocked carbachol-induced phase shifts at CT 6 (-11.6 ± 4.8 min; Mean phase shift ±S.E.M.) and CT 22 (-20 ± 6.6 min), suggesting that carbachol mediates its phase-shifting effects at these phases through muscarinic receptors.