Tolerance to morphine-induced hypoactivity in hamsters was investigated under conditions designed to test a Pavlovian conditioning model of morphine tolerance. One group of animals received i.p. injections of morphine (50 mg/kg) in the test environment and saline in the home cage; a second group received saline in the test environment and morphine in the home cage; a third group received saline in both environments. A subsequent morphine challenge in the test environment gave evidence of both associative and nonassociative tolerance. Associative tolerance was detectable 1 week later during a second morphine challenge. Compensatory hyperactivity, however, was not observed during a saline challenge in the presence of morphine-associated cues. Following the acquisition of tolerance, nonreinforced exposure to morphine-associated cues produced an attenuation of morphine tolerance (i.e., extinction of tolerance). The results are interpreted as providing partial support for the Pavlovian model and are discussed in terms of alternative associative models of tolerance.

No abstract