The role of CRF in the release of ACTH by opiate agonists and antagonists in rats.

Opiate agonists as well as opiate antagonists release adrenocorticotropic hormone (ACTH) through unknown central mechanisms. We examined the role of corticotropin releasing factor (CRF) in opioid actions on ACTH release. Rats were pretreated with a specific antiserum to rat CRF (r-CRF) prior to injection of the opiate antagonist naloxone or the opiate agonists morphine (mu-receptor agonist) or MR 2034 (kappa-receptor agonist). This abolished the increase in ACTH caused by naloxone or by the kappa-agonist. The mu-agonist morphine, however, caused a significant increase in ACTH in control- or r-CRF antiserum treated rats. We conclude that (a) endogenous opioids tonically inhibit the release of CRF, (b) kappa-agonists stimulate the release of CRF, and (c) mu-agonists release ACTH by acting additionally through CRF-independent mechanisms.