Electrophysiological basis of the reinforcing effects of cocaine

The meteoric rise in cocaine abuse over the past decade has led renewed interest in the mechanisms by which this drug produces it potent reinforcing effects. Animal studies have clearly implicated the mesoaccumbens and mesocortical dopamine (DA) neuronal systems as integral brain sites involved in mediating self-administration of cocaine. Biochemical studies have determined that the most reward-relevant action of cocaine within the brain is the inhibition of reuptake of synaptic DA which occurs as a result of cocaine binding to a site on the DA transporter. In this review, electrophysiological studies regarding the effects of cocaine on mesoaccumbens and mesocortical DA systems are presented and a comprehensive picture of how cocaine influences both individual neurons and total neurotransmission within these reward-relevant systems is offered. It is concluded that the powerful rewarding effects of cocaine may be related to its preferential actions at DA and serotonin nerve terminals within the nucleus accumbens and a relatively poor compensatory reduction of impulse generation in mesoaccumbens DA cells. The possibility that this hypothesis can be generalized to account for the rewarding effects of other drugs of abuse is also discussed.