Pharmacological inhibition of dopamine and serotonin activity blocks spontaneous and cocaine-activated behaviour

The dopaminergic (DA) and serotonergic (5-HT) systems are modulatory transmitter systems that can influence a wide range of behavioural functions. Psychostimulant drugs increase both DA and 5-HT activity by substance-specific mechanisms and, consequently, can broadly influence behavioural and emotional processes in humans and animals. In this chapter, we examine psychostimulant drug effects from the perspective of DA-5-HT and environmental context interactions and anchor this analysis to changes in spontaneous behaviour. In our consideration of the DA and 5-HT transmitter systems, we focus on pharmacological manipulations that target DA and 5-HT autoreceptors. Autoreceptors provide negative feedback inhibitory control of DA and 5-HT neuronal activity so that pharmacological treatments that act on autoreceptors can regulate DA and 5-HT availability. Since psychostimulant drug effects are linked to DA and 5-HT availability, our analysis focuses on investigations that use autoreceptor pharmacology to unravel the complexity of psychostimulant drug action. The overall findings from the experimental manipulations of autoreceptor pharmacology were then used to discuss issues pertinent to drug development for the treatment of psychostimulant drug addiction.