Sensitivity of mouse vas deferens to neurotransmitters: changes after morphine treatment

1. The pharmacological responses of the isolated vas deferens of the mouse were investigated after acute and chronic treatment with morphine. 2. The addition of morphine to the bath did not alter the responses of the vas deferens to exogenous noradrenaline, adrenaline or dopamine. 3. Low doses of morphine depressed the responses to acetylcholine. Very high concentrations of the opioid (8.5 x 10(-4) M) completely abolished, in about 50% of the preparations, the responses to exogenous acetylcholine, while in the other 50% a potentiation of the responses to low concentrations of acetylcholine was observed. 4. The vas deferens of mice chronically treated with morphine showed increased sensitivity to exogenous noradrenaline, but decreased sensitivity to acetylcholine. 5. A fresh amount of morphine added to the bath enhanced the responses of morphine-tolerant preparations to noradrenaline but not to dopamine or acetylcholine. The specificity of this phenomenon was demonstrated by the use of pentobarbitone instead of the opioid. 6. These results are in agreement with the theory that tolerance could result from a form of disuse supersensitivity.