2--hydroxy-5-9-dimethyl-2-allyl-6-7-benzomorphan and beta-funaltrexamine

The acute administration of morphine produces a characteristic increase in plasma corticosterone. By using the male rat with a chronic i.v. catheter, a stereotaxically placed cannula in the lateral ventricle and a sound-attenuated one-way vision chamber, the effects of prototypic kappa and sigma opiate receptor agonists were studied. Both ethyl-ketocyclazocine (EKC) and N-allyl-normetazocine [SKF 10047] (SKF) also produced such a rise in hormone level after i.v. or i.c.v. administration. The former effect was blocked by concurrent treatment with naloxone (NX), 0.4 mg/kg. The latter effect was not blocked by i.c.v. pretreatment with beta-funaltrexamine, a long-acting mu receptor antagonist, whereas the response to i.c.v. morphine was attenuated significantly. The development of acute dependence and short-term tolerance to EKC and SKF was also studied. Priming with either drug (i.v.) did not result in a NX-precipitated plasma corticosterone withdrawal response 3 hr later. Similar studies priming with morphine (i.c.v.) did result in the plasma corticosterone-elevated response when NX was administered i.c.v. after 3 hr. When EKC or SKF was substituted for morphine, no NX-induced response was observed. Short-term tolerance to the effects of EKC and SKF on the hypothalamo-pituitary-adrenal axis did not appear to occur. These data support the notion that stimulation of several subclasses of opiate receptors will result in the activation of the hypothalamo-pituitary-adrenal axis. Furthermore, it appears that the mu opiate receptor is involved in the initiation of acute opiate dependence.

Topics: Animals; Brain; Corticosterone; Cyclazocine; Ethylketocyclazocine; Humans; Hypothalamo-Hypophyseal System; Male; Morphine; Naloxone; Naltrexone; Opioid-Related Disorders; Phenazocine; Pituitary-Adrenal System; Rats; Rats, Inbred Strains; Receptors, Opioid; Receptors, Opioid, kappa; Receptors, Opioid, mu; Receptors, sigma