Pharmacological analysis of the rate-decreasing effects of mu and kappa opioids in pigeons

The present study investigated the rate-decreasing effects of several mu (morphine andl-methadone) and kappa (bremazocine, U69,593 and U50,488) opioid agonists in pigeons. Mu and kappa agonists were examined alone, in combination with naltrexone or the mu-selective opioid antagonist, -funaltrexamine (-FNA), and in pigeons treated chronically with U50,488. Naltrexone was equipotent in shifting the morphine,l-methadone and bremazocine dose-effect curves to the right, but was less potent in shifting the U69,593 dose-effect curve and did not shift the U50,488 dose-effect curve. -FNA shifted thel-methadone dose-effect curve to the right but did not shift the bremazocine, U69,593 or U50,488 dose-effect curves. Pigeons that developed tolerance to U50,488 following daily administration were cross-tolerant to bremazocine but not tol-methadone. Taken together, these experiments indicate that the rate-decreasing effects of morphine andl-methadone are mediated by mu opioid receptors, whereas the rate-decreasing effects of bremazocine, U69,593 and U50,488 in pigeons differ depending on the pharmacological procedures used to assess their effects.This work was supported by US Public Health Service Grant DA 02749 from the National Institute on Drug Abuse. L.A.D. is the recipient of Research Scientist Award DA 00033 and AJM of a Research Supplement for Minority Graduate Research Assistants. Portions of this research were submitted by the first author in partial fulfilment of the requirements for the degree of Doctor of Philosophy