In order to clarify the possible role of endogenous opioids in the sleep deprivation-induced syndrome, the effect of naloxone and various opioid agonists and antagonists was tested. As shown in Table 3, the administration of naloxone (1-10 mg/kg) reduced the latency to sleep in a dose-related manner. In contrast, morphine (1 and 5 mg/kg, i.p.), /3-endorphin and [D-Ala2,D-LeuS]enkephalin (DADLE), (2 and 1 /xg respectively, i.c.v.) markedly prolonged the insomnia following sleep deprivation (Fratta et al., 1987). Morphine-induced prolongation of the insomnia and behavioral stimulation in sleep-deprived animals could be antagonized by naloxone. The exact definition by which opioid receptor types might be involved in the above model of mania is still under investigation.