Emergence of altered circadian timing in a cholinergically supersensitive rat line.

Mammalian circadian rhythms are controlled by the suprachiasmatic nuclei (SCN) in concert with light information. Several neurotransmitters and neural pathways modulate light effects on SCN timing. This study used a line of rat with an upregulated cholinergic system to investigate the role of acetylcholine in rhythmicity. With the use of a selective breeding program based on the thermic response to a cholinergic agonist, we developed a supersensitive (S(ox)) and subsensitive (R(ox)) rat line. The S(ox) rats showed an earlier onset time of melatonin rhythm under a 12:12-h light-dark photoperiod from 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 lights on) compared with R(ox) animals (0.1 +/- 0.1 h). Furthermore, the S(ox) animals displayed a significantly shorter free-running period of temperature 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.