The purpose of the proposed studies is to identify and characterize the effects of certain abused 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 behaviorally effective doses of the same drugs can also affect the cardiovascular and thermoregulatory systems. Experiments will be conducted in squirrel monkeys surgically prepared under sterile conditions with chronically 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 as indices of cardiovascular activity, the direct measurement of colonic temperature as an index of thermoregulatory activity, and operantly conditioned psychomotor behavior as a measure of central nervous system activity. 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 are those that can have central-nervous-system stimulant effects and include cocaine, d-amphetamine, caffeine, nicotine and phencyclidine, and selected congeners. In addition, selected pharmacological agonists, antagonists and drugs that alter catecholamine or serotonin synthesis and uptake will be administered in combination with some of the drugs to study the pharmacological basis of the drug effects. The overall objective of the research program is to determine (1) the effects selected abused drugs with stimulant properties can have on the central nervous system of conscious nonhuman primates by studying the effects of the drugs on conditioned behavior in squirrel monkeys and chimpanzees, (2) the effects these drugs can have on heart rate, blood pressure and temperature at doses that have effects on behavior mediated via the central nervous system, and (3) whether the behavioral, cardiovascular or thermoregulatory effects can be enhanced, diminished or blocked by other drugs and chemical substances or by behavioral procedures.
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