The role of associative factors in tolerance to the hypothermic effects of morphine in mice.
Associative learning theories of drug tolerance emphasize the importance of stimuli which predict drug administration. One such model holds that drug tolerance is due to the development of a conditional response (CR) which is directionally opposed to the unconditional response (UCR) to the drug. By virtue of their opposing natures, the overlapping occurrence of CR and UCR is seen as a diminished response, i.e., tolerance. The present experiments tested the predictions of this model using two doses of morphine, and included truly random controls to examine the role of excitatory and inhibitory conditioning in tolerance. Tolerance was greatest in mice administered morphine in the context of stimuli previously paired with drug administration, intermediate in random controls, and least or absent in mice administered the drug in the presence of cues paired with vehicle injections. No direct evidence of a compensatory CR which could offset morphine's hypothermic effect was obtained in placebo test sessions, nor was evidence for such a response obtained in cross-drug tests with amphetamine and apomorphine.
D000818:Animals; D001245:Association Learning / Q000187:drug effects*; D001833:Body Temperature Regulation / Q000187:drug effects; D003213:Conditioning, Psychological / Q000187:drug effects; D004361:Drug Tolerance; D007035:Hypothermia / Q000139:chemically induced*; D007858:Learning / Q000187:drug effects*; D008297:Male; D051379:Mice; D009020:Morphine / Q000633:toxicity*
D009020:Morphine