Determining the region-specific contributions of 5-HT receptors to the psychostimulant effects of cocaine

Cocaine is a drug of abuse that has complex neurochemical and behavioural profiles. When it became evident that models that involve only dopamine do not fully explain the complex effects of cocaine on behaviour, the focus of research expanded to include the 5-hydroxytryptamine (5-HT) system in the brain. The 5-HT system comprises several subtypes of 5-HT receptors, which contribute differentially to the various behavioural effects of cocaine. In this article, we describe which subtypes regulate behaviours that are related to cocaine addiction and how they might provide new therapeutic approaches. Numerous subpopulations of each 5-HT receptor can be distinguished according to their location in the brain. We also discuss how these subpopulations relate to the effects of 5-HT-receptor stimulation at the systemic level. These insights provide a new receptor-based approach for understanding the 5-HT mechanisms that subserve the actions of cocaine and possible pharmacotherapies against cocaine addiction.