title: Emergence of altered circadian timing in a cholinergically supersensitive rat line.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Adelaide, Medical School, Adelaide, South Australia 5005. sferguso@medicine.adelaide.edu.au
authors.forename: S A
authors.initials: SA
authors.lastname: Ferguson
authors.forename: D J
authors.initials: DJ
authors.lastname: Kennaway
mesh_terms: D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D018678:Cholinergic Agents / Q000494:pharmacology*; D002940:Circadian Rhythm / Q000502:physiology*; D003624:Darkness; D004351:Drug Resistance; D008027:Light; D008550:Melatonin / Q000096:biosynthesis / Q000528:radiation effects; D018721:Muscarinic Agonists / Q000494:pharmacology; D010095:Oxotremorine / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats / Q000235:genetics* / Q000502:physiology*; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000378:metabolism
chemical_list: D018678:Cholinergic Agents; D018721:Muscarinic Agonists; D016760:Proto-Oncogene Proteins c-fos; D010095:Oxotremorine; D008550:Melatonin; D000109:Acetylcholine