title: Cross-tolerance and enhanced sensitivity to the response rate-decreasing effects of opioids with varying degrees of efficacy at the mu receptor.
abstract: The purpose of the present experiment was to determine whether the effects of opioids with varying degrees of efficacy at the mu receptor are differentially altered in morphine-tolerant pigeons. To this end, dose-effect curves were determined for high, intermediate, and low efficacy mu agonists in pigeons responding under a schedule of food presentation prior to, during, and after exposure to a regimen of chronic morphine administration. In pigeons treated with 56 mg/kg/daily morphine, the dose-effect curves for the rate-decreasing effects of the high-efficacy mu agonists morphine and fentanyl were shifted to the right of their prechronic positions (i.e., tolerance). A small degree of tolerance was also conferred to the intermediate-efficacy mu agonists (-)-pentazocine and (-)-metazocine, but not to nalbuphine or butorphanol. In contrast to the effects obtained with these mu agonists, the chronic morphine regimen shifted the dose-effects curves of the mu antagonist naloxone and the low-efficacy mu agonists nalorphine and levallorphan to the left of their prechronic positions (i.e., enhanced sensitivity). These findings demonstrate that morphine tolerance confers cross-tolerance to other high efficacy mu agonists, enhanced sensitivity to mu antagonists and low efficacy mu agonists, and little or no cross-tolerance to intermediate efficacy mu agonists. Disadvantages of using schedule-controlled responding to examine the effects of intermediate efficacy mu agonists are discussed.
authors.affiliation: Department of Psychology, University of North Carolina, Chapel Hill 27599-3270.
authors.forename: M J
authors.initials: MJ
authors.lastname: Picker
authors.forename: J
authors.initials: J
authors.lastname: Yarbrough
mesh_terms: D000818:Animals; D010856:Columbidae; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D007977:Levallorphan / Q000494:pharmacology; D009269:Nalorphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects*; D017450:Receptors, Opioid, mu
chemical_list: D009294:Narcotics; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D007977:Levallorphan; D009270:Naloxone; D009269:Nalorphine