INTRACEREBROVENTRICULAR INJECTION OF ISOPROTERENOL PRODUCES ITS ANALGESIC EFFECT THROUGH INTERLEUKIN-1-BETA PRODUCTION

The effects of isoproterenol, a beta-adrenoceptor agonist, on the prod uction of interleukin-lp in the brain and on mechanical nociception we re examined in rats. Intracerebroventricular (i.c.v.) injection of iso proterenol at the dose of 3 mu g/rat markedly induced interleukin-1 be ta mRNA in the molecular layer of the hippocampus, medial preoptic are a, paraventricular thalamic nucleus, paraventricular hypothalamic nucl eus, ventromedial hypothalamic nucleus, dorsomedial hypothalamic nucle us and central gray 1 h after injection. In these regions, interleukin -1 beta mRNA was expressed mainly in the glial cells. The thresholds t o the mechanical stimulation to the hind paw were elevated by i.c.v. a dministration of isoproterenol (1 to 10 mu g/rat). When isoproterenol was given at the dose of 3 mu g/rat, the analgesic effect showed two p eaks. The first peak was observed at 60 min after injection and the se cond was observed at 180 min. The second phase of analgesia was antago nized by coadministration of interleukin-l receptor antagonist. These results suggest that isoproterenol produces an analgesic effect, at le ast in part, through the induction of interleukin-1 beta expression in the brain. (C) 1997 Elsevier Science B.V.