Sensitivity to the discriminative stimulus and antinociceptive effects of mu opioids: Role of strain of rat, stimulus intensity, and intrinsic efficacy at the mu opioid receptor

Effects of low (butorphanol, nalbuphine)-, intermediate (buprenorphine)-, a nd high (morphine, levorphanol)-efficacy mu opioids were examined in F344, Sprague-Dawley (SD), Long-Evans (LE), and Lewis rats using a tail withdrawa l and a drug discrimination procedure. In the tail withdrawal procedure usi ng low (50 degrees C), intermediate (52 degrees C), and high (56 degrees C) water temperatures, morphine and levorphanol produced maximal effects in e ach of the strains and were most potent in F344 and least potent in Lewis, Similar differences across strains were obtained with buprenorphine, and at the high intensity, maximal effects were not obtained in Lewis. At the low intensity, butorphanol produced maximal effects in F344 and SD at relative ly low doses, half-maximal effects in LE at very high doses, and no effect in Lewis. Nalbuphine produced near maximal effects in F344 and SD when test ed with the low intensity and no effect in the LE and Lewis. Similar result s were obtained at the intermediate intensity for these opioids, although t he absolute level of antinociception was lower. These results indicate that there are profound differences to the antinociceptive effects of mu opioid s across rat strains. The magnitude of these differences increased with hig her stimulus intensities and when tested with lower efficacy opioids. In ra ts trained to discriminate morphine (3.0 or 5.6 mg/kg) from water, there we re no consistent differences across rat strains to the effects of these mu opioids. Possible reasons for differences between the results obtained in t he tail withdrawal and drug discrimination procedures are discussed.