Neurobiology of cocaine abuse

The recent escalation of cocaine abuse has increased awareness of the need to understand the behavioral effects of cocaine and the determinants of those effects. Cocaine alters both conditioned and unconditioned behavior, and has prominent reinforcing and subjective effects that are particularly relevant to its abuse. An increase in CNS dopamine neurotransmission, resulting from a competitive blockade of high-affinity dopamine uptake mediated by both D1 and D2 dopamine receptors, is a primary determinant of the behavioral effects of cocaine. Either tolerance or sensitization may develop with repeated administration of cocaine. Dependence also develops, although the behavioral changes associated with cocaine withdrawal are subtle. Although numerous CNS changes have been associated with repeated administration of cocaine, the neuropharmacological mechanisms that underlie the behavioral changes that occur with repeated administration remain to be firmly established. Bill Woolverton and Ken Johnson stress that continued collaboration between behavioral pharmacologists and neuroscientists is critical for a complete understanding of the effects of cocaine.