PT  - JOURNAL ARTICLE
AU  - Craft, R M
AU  - Picker, M J
AU  - Dykstra, L A
TI  - Differential cross-tolerance to opioid agonists in morphine-tolerant pigeons responding under a schedule of food presentation.
DP  - 1989 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 386--393
VI  - 249
IP  - 2
4099  - http://jpet.aspetjournals.org/content/249/2/386.short
4100  - http://jpet.aspetjournals.org/content/249/2/386.full
SO  - J Pharmacol Exp Ther1989 May 01; 249
AB  - Effects of the opioid agonists morphine, l-methadone, ethylketazocine, U50,488 [trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl]benzeneacetamide methanesulfonate hydrate], cyclazocine and bremazocine, and the nonopioid chlorpromazine were determined in pigeons responding under a fixed-ratio 30 schedule of food presentation before, during and after chronic morphine administration. Before chronic morphine administration, all drugs produced dose-dependent decreases in response rates. After daily administration of up to 56 mg/kg of morphine for 7 weeks, dose-effect curves for the mu agonists morphine and l-methadone, as well as the mu/kappa agonist ethylketazocine shifted to the right approximately 1 1/4, 3/4 and 1/2 log units, respectively. In contrast, dose-effect curves for the mixed agonist/antagonists cyclazocine and bremazocine each shifted to the left approximately 3/4 log unit, whereas dose-effect curves for the kappa agonist U50,488 and the nonopioid chlorpromazine did not shift during chronic morphine administration. Dose-effect curves for all drugs except bremazocine returned to their prechronic positions within the period 3 to 8 weeks after termination of chronic morphine administration. The present study demonstrates that repeated administration of morphine produces tolerance to its rate-decreasing effects as well as cross-tolerance selective to other opioids possessing mu agonist properties. The cross-tolerance to ethylketazocine observed in morphine-tolerant pigeons corroborates studies of the discriminative stimulus effects of ethylketazocine in pigeons, suggesting that in this species ethylketazocine possesses predominantly mu agonist properties.