1. ¹Department of Neurobiology of Rhythms, Institute of Cellular and Integrative Neurosciences, CNRS (UMR7168), University L. Pasteur, Strasbourg, France
2. ²Laboratory of Behavioural and Cognitive Neuroscience, CNRS (FRE2855), University L. Pasteur, Strasbourg, France
3. ³INSERM U666 (GRERCA) and Hôpitaux Universitaires de Strasbourg, Faculty of Medicine, Strasbourg, France

Correspondence: Dr L Pain, GRERCA, Unité 666 INSERM, Faculté de Médecine, 11 rue Humann, 67000 Strasbourg, France. Tel: +33 3 90 24 32 37/33 685436300; Fax: +33 3 90 24 32 56; E-mail: Laurepain@aol.com

⁴These authors contributed equally to the experiments.

Received 28 September 2005; Revised 15 February 2006; Accepted 28 February 2006; Published online 12 April 2006.

Abstract

Several common postdischarge symptoms, such as sleep disorders, headache, drowsiness or general malaise, evoke disturbances of circadian rhythms due to jet lag (ie crossing time zones) or shift work rotation. Considering that general anesthesia is associated with numerous effects on the central nervous system, we hypothesized that it may also act on the circadian timing system. We first determined the effects of the circadian timing on general anesthesia. We observed that identical doses of propofol showed marked circadian fluctuations in duration of effects, with a peak at the middle of the resting period (ie 7 h after lights on). Then, we examined the effects of general anesthesia on circadian timing, by analysing stable free-running circadian rhythms (ie in constant environmental conditions), an experimental approach used widely in circadian biology. Free-running rats were housed in constant darkness and temperature to assess possible phase-shifting effects of propofol anesthesia according to the time of the day. When administered around (2 h) the daily rest/activity transition point, a 30-min propofol anesthesia induced a 1-h phase advance in the free-running rest-activity rhythm, while anesthesia had no significant resetting effect at other times of the day. Anesthesia-induced hypothermia was not correlated with the phase-shifting effects of propofol anesthesia. From our results, anesthesia itself can reset circadian timing, and acts as a synchronizing cue for the circadian clock.