Cocaine abuse has been a persistent problem for over a decade. Despite efforts to understand the basis of cocaine's addictive properties, no pharmacotherapies have proven efficacious for human use. Inhibition of dopamine uptake in key brain reward circuits has been strongly linked to cocaines' behavioral-stimulant and reinforcing effects. Pharmacological manipulations of brain serotonin activity can modulate cocaine's profile of behavioral effects. The proposed studies seek to characterize the effects of selective serotonergic agents on the behavioral and reinforcing effects of cocaine and the selective dopamine uptake inhibitor, GBR 12909, in squirrel monkeys. Furthermore, microdialysis studies in awake, behaving squirrel monkeys will provide a unique approach to understanding the relationship between the behavioral consequences of cocaine self-administration and concurrent changes on brain neurochemistry that underlie cocaine's behavioral effects. Insights gained into the interactions between brain serotonin and dopamine systems will aid the understanding of cocaine abuse as well as numerous other conditions such as schizophrenia and depression which are believed to involve functional defects in these systems.
