Alpha-interferon inhibits adrenocortical secretion via mu 1-opioid receptors in the rat.
The effect of recombinant human alpha-interferon on plasma corticosterone concentrations was investigated in adult male rats. Intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration of alpha-interferon (10-10(4) U i.p., and 1-10(3) U i.c.v.) decreased basal plasma corticosterone concentrations. This effect was evident at both the peak and nadir in the circadian rhythm of hypothalamo-pituitary-adrenocortical secretory activity. The same inhibitory effect was obtained with intra-paraventricular nucleus administration of the cytokine. Furthermore, alpha-interferon attenuated the effects of stressors such as handling, 1 min of forced swimming, and sound stress in a novel environment. 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 microgram/kg), or of the mu 1-specific receptor antagonist, naloxonazine (1 microgram). The selective delta-opioid receptor antagonist, naltrindole (1 microgram i.c.v.) and the kappa-opioid receptor antagonist, nor-binaltorphimine (1 microgram i.c.v.) both failed to prevent the inhibitory effect of alpha-interferon (10(3) U i.p.) on adrenocortical secretion. The results obtained provide further evidence for a neuromodulatory effect of alpha-interferon and that this effect is mediated by central opioid receptors of the mu 1-subtype, delta- and kappa-opioid receptors not being involved.
Saphier
D
D
Department of Pharmacology, Louisiana State University Medical Center, Shreveport 71130-3932.
Welch
J E
JE
Chuluyan
H E
HE
D000818:Animals; D003345:Corticosterone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D016898:Interferon-alpha / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013550:Swimming
D016898:Interferon-alpha; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D009270:Naloxone; D009271:Naltrexone; C024524:beta-funaltrexamine; D003345:Corticosterone