Long-term effects of a tryptophan-free diet on serotonin metabolism and sleep-waking balance in rats.

1. A long-term (up to 16 weeks) tryptophan (TRP)-free diet was administered to chronically implanted adult rats in order to study the effects of a sustained reduction of endogenous brain serotonin (5-HT) levels on the sleep-waking cycle. Twenty-four hours polygraphic recordings were made either periodically on an EEG apparatus, or uninterruptedly over 50 days by a frequency analyser. Quantitative changes in wakefulness (W), slow wave sleep (SWS) and paradoxical sleep (PS), as well as the number and duration of these episodes, were studied over 24 h, with a dark period (DP) and a light period (LP). Biochemical changes in 5-HT metabolism were measured in both plasma and brain. 2. Under control conditions, the percentage of W was twice as great in DP as in LP, while the quantities of SWS and PS were twice as high in LP as in DP. Surprisingly, in spite of a decrease of about 50% in brain 5-HT under TRP-deprived conditions, no dramatic changes were observed in the qualitative or quantitative aspects of W, SWS or PS. The only electrocorticographic (ECoG) change was a disappearance of sleep spindles, which became total after 14 weeks. During the first month, there was a 7% increase in W accompanied by a 6% decrease in SWS and a 5-9% reduction in PS. Later, W and SWS returned to their control values, while the PS deficit persisted throughout the TRP-deprivation period. Despite the absence of severe quantitative disturbances over 24 h, an internal reorganization of the sleep cycle took place. This new balance, established after 2 months, was characterized by a tendency toward an equal distribution of the stages in DP and LP, resulting in the disappearance of the sleep circadian rhythm. 3. Our results are compared with those of other authors who lowered the endogenous 5-HT levels by various means, including 'acute' or partial TRP-deprivation. The present findings suggest that adaptive cerebral mechanisms are able to compensate for the disturbances in 5-HT metabolism, in structures responsible for W and SWS. They indicate that the neurohumoral processes underlying sleep circadian rhythm in the rat are serotoninergic and/or noradrenergic.