Changes in the rat sleep-wake cycle produced by DL-6-fluorotryptophan, a competitive inhibitor of tryptophan hydroxylase.

Abstract

DL-6-Fluorotryptophan (6-FT), a competitive inhibitor of tryptophan hydroxylase, produced a transient disruption of sleep in rats chronically implanted with EEG recording electrodes. In the 4 h period following the administration of 6-FT (120 mg/kg) awake time was increased, paradoxical sleep time was decreased and slow-wave sleep remained unchanged. These sleep changes were accompanied by significant reductions in brain 5-HT levels. L-Tryptophan (100 mg/kg) co-administration with 6-FT prevented the major sleep changes whereas L-leucine (100 mg/kg) was without effect. The major sleep changes produced by 6-FT were prevented by the pineal indole melatonin (20 mg/kg) but not by L-5-hydroxytryptophan (5 mg/kg). These neurochemical and drug interaction data raise the possibility that 5-hydroxytryptamine is involved in the control of paradoxical rather than slow-wave sleep in the rat.