The purpose of the proposed studies is to identify and characterize the effects of cocaine and related drugs on learned behavior and on physiological activity in nonhuman primates. The experiments are based on the outcome of previous studies in this laboratory showing that cocaine and other drugs with high abuse liability 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 some instances, with osmotic minipumps. Experiments will involve the direct measurements 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 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 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, methylphenidate and phencyclidine. In addition, selected pharmacological agonists, antagonists and drugs that alter catecholamine or serotonin synthesis and uptake or receptor activity will be administered in combination with cocaine and other drugs to study the pharmacological basis of the drug effects. Serum blood levels of drugs will be assayed using HPLC to describe the pharmacokinetics of the drugs under study and to correlate these findings with the behavioral and physiological 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 by studying the effects of the drugs on conditioned behavior in squirrel monkeys, (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, attenuated or blocked by other drugs and chemical substances or by behavioral procedures.
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