Journal of Pharmacology and Experimental Therapeutics 1999-05-01

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.

D Morgan, C D Cook, M J Picker

Index: J. Pharmacol. Exp. Ther. 289 , 965, (1999)

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Abstract

Effects of low (butorphanol, nalbuphine)-, intermediate (buprenorphine)-, and high (morphine, levorphanol)-efficacy mu opioids were examined in F344, Sprague-Dawley (SD), Long-Evans (LE), and Lewis rats using a tail withdrawal and a drug discrimination procedure. In the tail withdrawal procedure using low (50 degrees C), intermediate (52 degrees C), and high (56 degrees C) water temperatures, morphine and levorphanol produced maximal effects in each 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 relatively 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 tested with the low intensity and no effect in the LE and Lewis. Similar results were obtained at the intermediate intensity for these opioids, although the absolute level of antinociception was lower. These results indicate that there are profound differences to the antinociceptive effects of mu opioids across rat strains. The magnitude of these differences increased with higher stimulus intensities and when tested with lower efficacy opioids. In rats trained to discriminate morphine (3.0 or 5.6 mg/kg) from water, there were no consistent differences across rat strains to the effects of these mu opioids. Possible reasons for differences between the results obtained in the tail withdrawal and drug discrimination procedures are discussed.