The general objectives are to compare the tolerance that develops to the analgesic effects of morphine when drug delivery is reliably paired with distinctive cues (""""""""associative"""""""" tolerance) with the tolerance that develops in the absence of such cues (""""""""nonassociative"""""""" tolerance). The experiments are further intended to evaluate systematically certain predictions of a recently proposed theory, the habituation model of drug tolerance, which states that: (a) tolerance will be retained for longer periods of time if it is initially acquired under conditions which facilitate the association of cues with drug delivery, and (b) the contribution of associative tolerance to total tolerance magnitude will decline when drug administration procedures are employed that maximize the development of nonassociative tolerance. The studies are designed specifically to: (1) determine the impact of drug predictive cues on the magnitude of tolerance development to a moderate dose of drug administered at either short, intermediate, or long inter-dose intervals, (2) examine the retention of cued and uncued tolerance that develops under short or long inter-dose intervals, (3) discover is exposure to a drug dose prior to a conditioning trial disrupts the acquisition of associative tolerance, and (4) determine the relationship between dose level and magnitude of associative and nonassociative tolerance. In addition, the relationship between dose level and retention of tolerance that develops in the presence of distinctive cues will be examined. This research is relevant to psychopharmacology, experimental psychology, and pharmacology. The results of these studies may have direct implications for the development of drug tolerance and dependence in drug abusers. The data will also have relevance for the application of various theories of drug conditioning to the clinical use of opiates, particularly with regard to the conditions which may facilitate or retard the development of tolerance.
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