This is a proposal to continue basic research on the capacity of a wide variety of drugs to modify the reinforcing effects of cocaine. We have, in the past two years, developed a procedure that allows rapid evaluation of the reinforcing effects of intravenously delivered cocaine or other drugs in the rhesus monkey. In this procedure, monkeys can respond on a lever and receive intravenous infusions of cocaine during twice-daily sessions. During each session, four different infusion durations are used to provide access to four different doses of cocaine. The pump durations and drug concentrations used result in a positive relation between dose of cocaine and rate of responding. This paradigm has proven useful in evaluating the effects of several dopamine antagonists on cocaine's reinforcing effects, and should continue to produce information on the relationship between activation and blockade of dopamine receptors and drug-reinforced responding. We plan to supplement this research with studies of interactions of various dopamine agonists and antagonists on food- reinforced responding in the mouse. In addition, we would like to continue the aims of the original grant to study the effects of a wide variety of drugs on behavior maintained by cocaine. These will include anticholinergic, antiparkinson, antidepressant, and antihypertensive drugs, in addition to further studies of antipsychotic drugs, and other drugs that have promise in the treatment of cocaine abuse. The need for pharmacological treatment are quite slim. Further research on the pharmacological mechanisms of cocaine abuse may prove quite helpful in suggesting ways in which the reinforcing effects of cocaine might be reduced, and studies on a wide range of pharmacological agents may reveal useful drugs that might otherwise be overlooked.
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