Drug abuse remains a national problem of major proportions. Innumerable clinical reports and case studies document the personal tragedy that has befallen many persons. The increasing frequency of reports of cocaine abuse and cocaine-induced deaths, for example, has dramatized the dangers associated with that drug. The purpose of the studies proposed in this application is to identify and characterize the effects of cocaine and selected drugs on learned behavior and on physiological systems in two species of nonhuman primates. The experiments are based on the outcome of previous studies in this laboratory showing that many drugs with high abuse liability can have pronounced effects on behavior and that behavioraly - effective doses of the same drugs can also effect the cardiovascular and thermoregulatory systems. Experiments will be conducted in squirrel monkeys surgically prepared with indwelling arterial and venous catheters and in chimpanzees trained to accept intramuscular injections. Protocols will utilize the direct measurement of systemic arterial blood pressure and heart rate, the direct measurement of colonic temperature and operantly-conditioned psychomotor behavior. A wide range of doses of selected drugs will be administered alone to determine the direction, magnitude and time course of the effects on heart rate, blood pressure and temperature during periods of rest, and on behavioral and physiological activity during periods of ongoing schedule-controlled behavior. Drugs of primary interest include cocaine, d-amphetamine, caffine and nicotine. In addition, drugs that selectively block neurotransmitter uptake or that block catecholamine or serotonin receptors with high specificity will be administered in combination with cocaine and other drugs to study the pharmacological basis of the drug effects. Finally, neurotransmitter levels will be measured in vivo using a microdialysis technique. The overall objective of the research program is to determine (1) the effects cocaine and selected drugs can have on the behavior of conscious nonhuman primates, (2) the effects these drugs can have on heart rate, blood pressure and temperature at doses that have effects on behavior, and (3) whether the behavioral, cardiovascular or thermoregulatory effects can be diminished or blocked by other drugs and chemical substances or by behavioral procedures.
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