INTERFERON INDUCES SLEEP AND OTHER CNS RESPONSES IN MICE RECOVERING FROM HEXOBARBITAL ANESTHESIA

Immediately after recovery from hexobarbital anesthesia, mice were inj ected intraperitoneally with one of the following interferons: natural mouse alpha/beta, recombinent mouse (rmouse gamma IFN-A) or human alp ha A, alpha D, alpha AD interferon (rHu alpha IFN-A, rHu (alpha IFN-D, rHu alpha IFN-AD). All of these interferons, except rHu alpha IFN-A i nduced unconsciousness (''sleep''); all produced stimulatory effects t hat mimicked those produced by morphine in the mouse. Quantifiation of the duration of sleep, induced by rmouse gamma IFN, was investigated and found to be dose-related. Only 3 of the 5 interferons (mouse alpha /beta IFN, rmouse gamma IFN, rHu alpha IFN-AD) possesses antiviral act ivity and depresses the cytochrome P-450 system in the mouse, yet all 5 of the interferons produced CNS effects. This partition of effects, together with the very short latency of the interferon-induced CNS eff ects, shows that the CNS effects were mechanistically independent of t he anti-viral and anti-cytochrome P-450 effects. This disparity of the actions of the interferons suggests the possibility that selected mor phine antagonists could be used to counter some of the dose-limiting C NS effects of the large doses of interferons used in clinical situatio ns.