Goals of the proposed research are to use a rhesus monkey model of drug abuse, to study factors affecting vulnerability to drug abuse and to evaluate behavioral and pharmacological treatment interventions. Routes of administration that have been developed in this laboratory will include oral drug self-administration and smoking. When using the oral route of self-administration, liquid deliveries are contingent upon lip-contact responses. Smoke deliveries are contingent upon inhalation responses. Vulnerability factors to be examined are sex and phase of the menstrual cycle as well as patterns/duration of access to drugs. Initial work indicates that escalation from drug use to abuse is dependent upon the amount and duration of access. The proposed work will extend these findings to monkeys, other drugs, and measures of reinforcing efficacy. In addition, the question of whether differential access to one drug affects acquisition of self-administration of a second drug will be examined. Well-accepted measures of the reinforcing efficacy of drugs, behavioral economic demand curve analyses and PR schedules will be used to determine how these predisposing factors ultimately affect the reinforcing potential of selected drugs. The drugs that will be studied are cocaine, ethanol, heroin, methadone and phencyclidine (PCP). Behavior maintained by food and/or liquid saccharin will be used as a control for drug-selective effects. The behavioral economic measures will also be used quantify the extent to which these drug and nondrug substances substitute for each other. These studies will inform us about the effectiveness of substituting nondrug items for drugs in treatment, as well for predicting polydrug abuse by how well one form of drug abuse substitutes for another. The use of nondrug reinforcers as a behavioral treatment will also be compared in male and female monkeys and during 3 phases of the menstrual cycle. Potential treatment medications will also be examined in male monkeys using a behavioral economic approach. Three different types of drugs that have produced promising preliminary results are proposed: bremazocine, an agonist at the kappa opioid receptor, baclofen, a GABAB agonist, and ketoconazole, an inhibitor of corticosterone synthesis. Finally, the behavioral (alternative reinforcer) and pharmacological treatments will be combined and compared to the effects of each given alone. The results of the proposed 11 experiments will provide valuable information about major vulnerability factors and several behavioral and pharmacological treatment approaches for drug abuse. It is hoped that this information will lead to earlier and more effective prevention and treatment of drug abuse.
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