Environmental control of morphine tolerance in the hamster

Abstract

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.

Responding Changes Systematically Within Sessions During Conditioning Procedures

“…First, although unconditioned behavior pat-terns usually decrease across the session, increases (e.g., Montgomery, 1955) or bitonic functions have also been reported (Bindra & Spinner, 1958;Blanchard & Blanchard, 1971;Bronstein, Neiman, Wolkoff, & Levine, 1974;Chiszar, Wellborn, Wand, Scudder, & Smith, 1980;Davis & Astrachan, 1978;Schnur & Martinez, 1989; W. Thompson & Solomon, 1954). For example, Davis (1974aDavis ( , 1974b reported that startle responses elicited by a tone decreased with successive tone presentations when the tone was 120 dB, regardless of background noise.…”

Coordinated activity of a central pathway drives associative opioid analgesic tolerance

“…Accumulating evidence has emerged to suggest that learning processes play an essential role in the development of tolerance to the analgesic effect of opioids. For instance, a large amount of animal studies show that rodents administered with morphine in a distinctive context displayed a higher degree of morphine tolerance than the animals given morphine in a home cage (14)(15)(16)(17)(18)(19)(20). This associative opioid analgesic tolerance (AOAT) can also make a clinical impact on the analgesic efficacy in the treatment of patients with chronic pain (21).…”