Twelve monkeys will receive daily access (for 3 hr) to phencyclidine contingent upon lip-contact responses. Experiments are designed to identify and describe factors that either increase or decrease PCP-reinforced behavior. Food deprivation has recently been shown to produce marked increases in drug self-administration. It is theoretically and clinically important to examine the underlying mechanisms of a variable that has such powerful control over the establishment and persistence of drug-rewarded behavior. One hypothesis that will be tested in regard to this effect is that food deprivation increases the reinforcing efficacy of the drug. Concurrent choice procedures will be used with PCP and nondrug reinforcers and with two PCP concentrations. Another hypothesis to be tested is that interoceptive stimuli associated with food deprivation function as discriminative stimuli and/or conditioned reinforcers to amplify the maintenance and elicit the relapse of drug-seeking behavior. Orectic (e.g., 2-deoxy-D-glucose) and anorectic drugs (e.g., naloxone) will be given to provide stimuli comparable to food deprivation and satiation, and their effects on PCP-reinforced behavior will be assessed. In another experiment intermittent exposure to food-deprivation will be given after PCP access has terminated to determine whether these conditions reinstate high rates of drug-seeking behavior. To determine whether the food-deprivation effect is based on specific nutritional deficits or loss of an alternative reinforcer, dietary components (e.g., calories, protein, carbohydrates, vitamins) will be reduced, but cellulose will be added to keep the total volume of available food constant. Another variable that is related to the persistence of PCP-rewarded behavior is the development of physical dependence. A general issue that will be pursued concerns the effect of a mild abstinence syndrome produced by one drug (e.g., PCP) on behavior reinforced by another drug. This interaction has received little attention in the literature, but may have considerable significance for those who abuse multiple substances. Finally, laboratory studies of drug self-administration have focused upon the establishment of animal models of drug abuse, very few have focused upon methods to reduce drug-taking behavior. The proposed experiments will study the effectiveness of presenting alternative reinforcers along with PCP under concurrent independently operating behavioral schedules. Related experiments will evaluate the effectiveness of brief stimuli associated with alternative reinforcers on PCP-reinforced behavior. A final study will assess the physiological effects of long-term phencyclidine use.
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