Opiate antagonist--receptor interaction unchanged by acute or chronic opiate treatment.

The apparent pA2 of naloxone, a measure of the apparent receptor affinity for the antagonist, was estimated in naive rats, in rats after acute and various schedules of chronic morphine pretreatment, and in rats during abrupt withdrawal. The results were adjusted to compensate for the amount of pretreatment drug in the rat brains as, otherwise, such a drug could have inflated the apparent pA2 values (see appendix). After this adjustment, a tendency of the apparent pA2 values to be increased after chronic pretreatment disappeared. The apparent pA2 of naloxone in acutely pretreated rats was also unchanged from that in naive rats, while the results in abruptly withdrawn rats were ambiguous. Thus, no change in the affinity of the antagonist for opiate receptors was found and theories suggesting that a conformational change takes place in the opiate receptor during the development of tolerance/dependence could not be supported.