INTRACISTERNAL ADMINISTRATION OF INTERLEUKIN-1-BETA ATTENUATES NALOXONE-PRECIPITATED WITHDRAWAL IN MORPHINE-DEPENDENT

The effect of central administration of interleukin-1 beta on naloxone -precipitated withdrawal in morphine-dependent mice was studied. The d egree of physical dependence on morphine was estimated by counting the number of jumps precipitated by naloxone, one of the typical withdraw al signs. Intracisternal (i.c.) administration of interleukin-1 beta ( 0.01-1 ng/5 mu l per mouse) to morphine-dependent mice 30 min prior to the injection of naloxone (10 mg/kg i.p.) decreased the number of jum ps in a dose-dependent manner. The effect of interleukin-1 beta (1 ng) was significantly antagonized when it was co-administered with interl eukin-1 receptor antagonist (1 mu g/mouse). These results suggest that centrally administered interleukin-1 beta could attenuate naloxone-pr ecipitated withdrawal in morphine-dependent mice via interleukin-1 rec eptors in the brain. Go-administration of alpha-melanocyte-stimulating hormone (300 ng/mouse) or alpha-helical corticotropin-releasing facto r (CRF)-(9-41), a CRF receptor antagonist (300 ng/mouse), with interle ukin-1 beta also antagonized the inhibitory effect of interleukin-1 be ta (1 ng). Moreover, i.c. administration of CRF (200 ng/mouse) signifi cantly decreased the number of jumps.