5-Hydroxytryptophan, but not L-tryptophan, alters sleep and brain temperature in rats.
The precise role of serotonin (5-hydroxytryptamine) in the regulation of sleep is not fully understood. To further clarify this role for 5-hydroxytryptamine, the 5-hydroxytryptamine precursors L-tryptophan (40 and 80 mg/kg) and L-5-hydroxytryptophan (25-, 50-, 75-, 100 mg/kg) were injected intraperitoneally into freely behaving rats 15 min prior to dark onset, and subsequent effects on sleep-wake activity and cortical brain temperature were determined. 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 delayed increase in non-rapid eye movement sleep in post-injection hours 3-12. These highest doses inhibited non-rapid eye movement sleep during the subsequent 12-h light period. The finding that L-5-hydroxytryptophan, but not L-tryptophan, induced a dose-dependent and long-lasting decrease in cortical brain temperature regardless of whether or not non-rapid eye movement sleep was suppressed or enhanced contributes to a growing list of conditions showing that sleep-wake activity and thermoregulation, although normally tightly coupled, may be dissociated. The initial non-rapid eye movement sleep inhibition observed following low doses of L-5-hydroxytryptophan may be attributable to increased serotonergic activity since 5-hydroxytryptamine may promote wakefulness per se, whereas the delayed non-rapid eye movement sleep enhancement after higher doses may be due to the induction by 5-hydroxytryptamine of sleep-inducing factor(s), as previously hypothesized. The period of non-rapid eye movement sleep inhibition beginning 12 h after administration of L-5-hydroxytryptophan doses that increase non-rapid eye movement sleep is characteristic of physiological manipulations in which non-rapid eye movement sleep is enhanced. The results of the present study suggest that the complex effects of 5-HT on sleep depend on the degree and time course of activation of the serotonergic system such that 5-HT may directly inhibit sleep, yet induce a cascade of physiological processes that enhance subsequent sleep.
Imeri
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Department of Psychiatry and Behavioral Sciences, University of Texas Medical Branch, Galveston 77555-0431, USA.
Mancia
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Bianchi
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Opp
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MR
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects*; D001833:Body Temperature Regulation / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D004569:Electroencephalography / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology*; D012895:Sleep, REM / Q000187:drug effects*; D014364:Tryptophan / Q000494:pharmacology*; D014851:Wakefulness / Q000187:drug effects
D012701:Serotonin; D014364:Tryptophan