Effect of opioid receptor antagonists on hypothalamic-pituitary-adrenal activity in rhesus monkeys.
Some opioid antagonists increase the release of adrenocorticotropic hormone (ACTH) and cortisol in humans and, therefore, may indicate that endogenous opioids modulate hypothalamic-pituitary-adrenal axis activity. The type of opioid receptor that may be related to these endocrine effects is unknown. The purpose of this experiment was to evaluate the ability of different opioid antagonists to increase ACTH and cortisol plasma levels in rhesus monkeys. Eight monkeys received intramuscular injections of various antagonists: 0.0032-1.0 mg/kg naltrexone, 0.1-3.2 mg/kg naltrindole (delta-selective), 0.032-0.32 mg/kg clocinnamox (mu-selective), and 1-3.2 mg/kg nor-binaltorphimine (kappa-selective). Naltrexone, 0.1-1.0 mg/kg, increased ACTH levels, whereas naltrindole and clocinnamox failed to increase ACTH levels. Nor-binaltorphimine, 1-3.2 mg/kg, increased ACTH concentrations on the day of injection, but not at a time when other assays continue to demonstrate kappa-antagonism (24 h). Cortisol concentrations generally followed the same pattern as the ACTH concentrations, but the incremental differences in cortisol release between doses were less clear. Thus, opioid modulation of ACTH and cortisol plasma levels is not clearly associated with a particular opioid receptor. Although the kappa-antagonist increased ACTH and cortisol release on the day of injection, some evidence suggests that this endocrine effect may be due to mechanisms other than those mediated by the kappa-receptor. Alternatively, the naltrexone-induced increase of ACTH and cortisol plasma levels may be caused by activity at multiple opioid receptors or some uncharacterized receptor. Finally, the increased release of ACTH and cortisol may be a response to naltrexone's aversive properties.
Williams
K L
KL
Department of Psychology, Grand Valley State University, 2224 Au Sable Hall, 1 Campus Dr, Allendale, MI 49401, USA. willikei@gvsu.edu
Ko
M C Holden
MC
Rice
K C
KC
Woods
J H
JH
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000187:drug effects*; D000818:Animals; D002934:Cinnamates / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008253:Macaca mulatta; D008297:Male; D009022:Morphine Derivatives / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000187:drug effects*
D002934:Cinnamates; D009022:Morphine Derivatives; D009292:Narcotic Antagonists; C076806:clocinnamox; C051844:norbinaltorphimine; D009271:Naltrexone; D000324:Adrenocorticotropic Hormone; C055382:naltrindole; D006854:Hydrocortisone