5-hydroxytryptophan, but not L-tryptophan, alters sleep and brain temperature in rats

The precise role of serotonin (5-hydroxytryptamine) in the regulation of sl eep is not fully understood. To further clarify this role for 5-hydroxytryp tamine, the 5-hydroxytryptamine precursors L-tryptophan (40 and 80 mg/kg) a nd L-5-hydroxytryptophan (25-, 50-, 75-, 100 mg/kg) were injected intraperi toneally into freely behaving rats 15 min prior to dark onset, and subseque nt effects on sleep-wake activity and cortical brain temperature were deter mined. L-5-hydroxytryptophan, but not L-tryptophan, induced dose-dependent changes in sleep-wake activity. During the 12-h dark period, non-rapid eye movement sleep was inhibited in post-injection hours 1-2 by the two lowest L-5-hydroxytryptophan doses tested, while the two highest doses induced a d elayed increase in non-rapid eye movement sleep in post-injection hours 3-1 2. These highest doses inhibited non-rapid eye movement sleep during the su bsequent 12-h light period. The finding that L-5-hydroxytryptophan, but not L-tryptophan, induced a dose-dependent and long-lasting decrease in cortic al brain temperature regardless of whether or not non-rapid eye movement sl eep was suppressed or enhanced contributes to a growing list of conditions showing that sleep-wake activity and thermoregulation, although normally ti ghtly coupled, may be dissociated. The initial non-rapid eye movement sleep inhibition observed following low doses of L-5-hydroxytryptophan may be at tributable to increased serotonergic activity since 5-hydroxytryptamine may promote wakefulness per se, whereas the delayed non-rapid eye movement sle ep enhancement after higher doses may be due to the induction by 5-hydroxyt ryptamine of sleep-inducing factor(s), as previously hypothesized. The peri od of non-rapid eye movement sleep inhibition beginning 12 h after administ ration of L-5-hydroxytryptophan doses that increase non-rapid eye movement sleep is characteristic of physiological manipulations in which non-rapid e ye movement sleep is enhanced. The results of the present study suggest that the complex effects of 5-HT o n sleep depend on the degree and time course of activation of the serotoner gic system such that 5-HT may directly inhibit sleep, yet induce a cascade of physiological processes that enhance subsequent sleep. (C) 1999 IBRO. Pu blished by Elsevier Science Ltd.