Emergence of altered circadian timing in a cholinergically supersensitive rat line

Mammalian circadian rhythms are controlled by the suprachiasmatic nuclei (S CN) in concert with light information. Several neurotransmitters and neural pathways modulate light effects on SCN timing. This study used a line of r at with an upregulated cholinergic system to investigate the role of acetyl choline in rhythmicity. With the use of a selective breeding program based on the thermic response to a cholinergic agonist, we developed a supersensi tive (S-ox) and subsensitive (R-ox) rat line. The S-ox rats showed an earli er onset time of melatonin rhythm under a 12:12-h light-dark photoperiod fr om generation 3 (3 +/- 0.5 h after dark) compared with R-ox rats (4.5 +/- 0 .1 h) and an earlier morning decline in temperature (0.9 +/- 0.3 h before l ights on) compared with R-ox animals (0.1 +/- 0.1 h). Furthermore, the S-ox animals displayed a significantly shorter free-running period of temperatu re rhythm than R-ox rats (23.9 +/- 0.04 and 24.3 +/- 0.1 h, respectively, P < 0.05). The results suggest that the altered circadian timing of the S-ox rats may be related to the cholinergic supersensitivity, intimating a role for acetylcholine in the circadian timing system.