Circadian variation in behavioural responses to central 5-HT receptor stimulation in the mouse.

The intensity of head-twitch and the 5-HT syndrome (tremor, fore-paw treading, head-weaving, hind-limb abduction) was measured in male CFLP mice after injection of 5 mg/kg 5-MeODMT. Head-twitch showed a clear circadian variation, with highest scores mid-light, but no circadian variation in the 5-HT syndrome was observed. Dose-response curves for 5-MeODMT (2-64 mg/kg) confirmed the head-twitch difference, with a parallel rightward shift for mid-dark versus mid-light up to 32 mg/kg, while no difference appeared for the 5-HT syndrome. Time-course measurements showed no differences between mid-light and mid-dark, making pharmacokinetic explanations unlikely. The circadian rhythm in head-twitch but not in the 5-HT syndrome suggests these behaviors are mediated by different 5-HT receptor subtypes.

Study at a glance

Abstract

The intensity of the head-twitch response and the 5-hydroxytryptamine (5-HT) syndrome (tremor, fore-paw treading, head-weaving and hind-limb abduction) was measured in male CFLP mice following IP injection of 5 mg/kg 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). The results of separate experiments carried out at 1.5-h intervals throughout the light-dark cycle showed a clear circadian variation in head-twitch, with highest scores mid-light. No circadian variation in the 5-HT syndrome, or in any individual element of it, was observed. Dose-response curves constructed for 5-MeODMT mid-light and mid-dark over the range 2-64 mg/kg IP confirmed the difference in head-twitch response, showing a parallel shift to the right for mid-dark compared to mid-light up to 32 mg/kg. Again, no difference was seen between the two curves for the 5-HT syndrome. Measurement of the time course of behavioural activity following 5-MeODMT failed to show any differences between mid-light and mid-dark, making it unlikely that pharmacokinetic differences account for the observed circadian variation. It is suggested that the demonstration of a circadian rhythm in the head-twitch response and the failure to show any comparable rhythm in the 5-HT syndrome provides further evidence that these behaviours are mediated by different 5-HT receptor subtypes.