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.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Emory University
Primate Centers
United States
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Howell, L L; Schama, K F; Ellis, J E et al. (2001) Fetal development in rhesus monkeys exposed prenatally to cocaine. Neurotoxicol Teratol 23:133-40
Howell, L L; Czoty, P W; Kuhar, M J et al. (2000) Comparative behavioral pharmacology of cocaine and the selective dopamine uptake inhibitor RTI-113 in the squirrel monkey. J Pharmacol Exp Ther 292:521-9
Czoty, P W; Justice Jr, J B; Howell, L L (2000) Cocaine-induced changes in extracellular dopamine determined by microdialysis in awake squirrel monkeys. Psychopharmacology (Berl) 148:299-306
Bakay, R A; Boyer, K L; Freed, C R et al. (1998) Immunological responses to injury and grafting in the central nervous system of nonhuman primates. Cell Transplant 7:109-20
Schama, K F; Howell, L L; Byrd, L D (1997) Serotonergic modulation of the discriminative-stimulus effects of cocaine in squirrel monkeys. Psychopharmacology (Berl) 132:27-34
Howell, L L; Czoty, P W; Byrd, L D (1997) Pharmacological interactions between serotonin and dopamine on behavior in the squirrel monkey. Psychopharmacology (Berl) 131:40-8
Howell, L L; Coffin, V L; Spealman, R D (1997) Behavioral and physiological effects of xanthines in nonhuman primates. Psychopharmacology (Berl) 129:1-14
Howell, L L; Landrum, A M (1997) Effects of chronic caffeine administration on respiration and schedule-controlled behavior in rhesus monkeys. J Pharmacol Exp Ther 283:190-9
Howell, L L; Byrd, L D (1995) Serotonergic modulation of the behavioral effects of cocaine in the squirrel monkey. J Pharmacol Exp Ther 275:1551-9
Howell, L L (1995) Effects of caffeine on ventilation during acute and chronic nicotine administration in rhesus monkeys. J Pharmacol Exp Ther 273:1085-94

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