ALPHA-INTERFERON INHIBITS ADRENOCORTICAL SECRETION VIA MU(1)-OPIOID RECEPTORS IN THE RAT

The effect of recombinant human alpha-interferon on plasma corticoster one concentrations was investigated in adult male rats. Intraperitonea l (i.p.) or intracerebroventricular (i.c.v.) administration of alpha-i nterferon (10-10(4) U i.p., and 1-10(3) U i.c.v.) decreased basal plas ma corticosterone concentrations. This effect was evident at both the peak and nadir in the circadian rhythm of hypothalamo-pituitary-adreno cortical secretory activity. The same inhibitory effect was obtained w ith intra-paraventricular nucleus administration of the cytokine. Furt hermore, alpha-interferon attenuated the effects of stressors such as handling, 1 min of forced swimming, and sound stress in a novel enviro nment. The effect of alpha-interferon (10(2) U i.c.v.) was blocked by prior injection of the opioid receptor antagonist, naloxone (1 mg/kg i .p.). Similarly, the effect of 10(3) U alpha-interferon administered i .p. was blocked by i.c.v. injection of naloxone (1 mug/kg), or of the mu1-specific receptor antagonist, naloxonazine (1 mug). The selective delta-opioid receptor antagonist, naltrindole (1 mug i.c.v.) and the k appa-opioid receptor antagonist, nor-binaltorphimine (1 mug i.c.v.) bo th failed to prevent the inhibitory effect of alpha-interferon (10(3) U i.p.) on adrenocortical secretion. The results obtained provide furt her evidence for a neuromodulatory effect of alpha-interferon and that this effect is mediated by central opioid receptors of the mu1-subtyp e, delta- and kappa-opioid receptors not being involved.