BEHAVIORAL TOLERANCE AND CROSS-TOLERANCE TO THE RESPONSE RATE-DECREASING EFFECTS OF MU-OPIOID IN RATS

The present study was designed to characterize the degree of cross-tol erance between the response rate-decreasing effects of morphine and th ree mu opioids with varying relative intrinsic efficacies at the ma re ceptor, buprenorphine, butorphanol and fentanyl, and a non-opioid (+)- amphetamine, in a behavioral-tolerance paradigm, Lever pressing of rat s was maintained by a fixed-ratio 20 schedule of food presentation, an d dose-effect curves for each drug were obtained prior to, during, and after daily administrations of morphine in separate groups of rats ad ministered morphine either before (pre-session) or after (post-session ) experimental sessions. Each of the ma opioids and the non-opioid (+) -amphetamine dose-dependently decreased response rates. In the pre-ses sion group, daily administration of morphine shifted the morphine dose -effect curve 0.33 log unit rightward, indicating that tolerance had d eveloped, and shifted the butorphanol dose-effect curve 0.96 log unit rightward. Daily pre-session administrations of morphine did not shift the dose-effect curves for buprenorphine, fentanyl, or (+)amphetamine . In the post-session group, daily administration of morphine did not shift the morphine, butorphanol, buprenorphine, fentanyl, or (+)-amphe tamine dose-effect curves. These data suggest that pharmacological var iables, such as the drug's relative intrinsic efficacy at the mu recep tor, can play a role in behavioral tolerance and cross-tolerance.