Serotonin as an important mediator of cocaine's behavioral effects

Abstract

Although the dopaminergic system still plays an important role in the investigation of the behavioral effects of cocaine, a broad literature emerged parallel to this research that provided significant evidence for an important contribution of the serotonergic (5-hydroxytryptamine, 5-HT) system. It has been known for a long time that the 5-HT transporter is one of the primary targets of cocaine within the brain and that cocaine causes an increase in the 5-HT activity in many brain regions. In general, the 5-HT system plays an important role in the organization of spontaneous behaviors, like locomotion, eating, drinking or grooming, and is also involved in emotion and mood. This review provides an overview of the role of 5-HT and 5-HT receptors in the acute behavioral and subjective effects of cocaine. There is broad evidence for a contribution of the 5-HT system to cocaine-induced hyperactivity in animals and to the subjective hedonic effects in humans. Studies with selective 5-HT receptor-ligands suggest the contribution of a large number of different 5-HT receptor subtypes to these effects. In order to fully understand the behavioral effects of cocaine and the mechanisms of their mediation, the 5-HT system needs to be considered, either parallel to or in interaction with the dopaminergic system.