The Serotonergic System May Be Involved in the Sleep-inducing Action of Oleamide in Rats

The mechanism underlying the sleep-inducing effect of oleamide, an endogenous fatty acid amide, was studied in rats. Animals implanted with cerebrocortical and dorsal neck muscle electrodes were monitored continuously by electroencephalograph (EEG) and electromyograph (EMG) for 4 h after i.p. or s.c. injection of drugs. Oleamide induced a dose-dependent increase in slow-wave sleep (SWS), a decrease in wakefulness (W) and sleep latency, but had no effect on rapid-eye-movement sleep (REMS). The oleamide-induced increase in SWS was prevented by 5-HT reuptake inhibitors such as fluoxetine or fenfluramine and by agonists at 5-HT(1A) receptors such as buspirone or 8-hydroxy-2-(di- N-propylamino) tetralin (8-OH-DPAT). Moreover, the selective 5-HT(1A) receptor antagonist WAY100635 markedly antagonized the suppression of the oleamide-induced increase in SWS by 8-OH-DPAT. These data provide the first behavioural evidence that the serotonergic system may be involved in the sleep-inducing action of oleamide in rats.