Abstract

L-5-Hydroxytryptophan (5-HTP), the precursor of serotonin, has phase-resetting ability under constant conditions in mammals. However, it is not known whether it can entrain a free-running rhythm. We report that 5-HTP (50 mg/kg) entrains the free-running rhythm of Mus terricolor to 24 h, when presented once in 24 h at zeitgeber time (ZT) 6, corresponding to its previously known circadian time (CT) of maximum advance in complete darkness (CT 6), on the last pre-intervention day. This entrainment is accompanied by shortening of the period and visible after withdrawal of injections. After-effects may persist for a few days. The mechanistic explanation is currently unknown, but this probably occurs through serotonergic phase and period modifications. 5-HTP is thus potentially useful as a chronobiotic in circadian rhythm disorders.

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