Psychostimulant drugs and a dopamine hypothesis regarding addiction: update on recent research

Evidence that psychostimulant drugs interact principally with monoamines, and in particular with the mesolimbic pathway that utilizes dopamine as the neurotransmitter, has prompted the dopamine hypothesis of psychostimulant addiction. This hypothesis proposes that enhancement of dopamine neurotransmission in the mesolimbic pathway is fundamental to the reinforcing properties of many drugs of abuse. Cocaine, the best characterized psychostimulant, is seen to fulfil this hypothesis by blocking dopamine transporters, thereby preventing re-uptake of the neurotransmitter and enhancing its synaptic concentration (Fig. 1). This biochemical mechanism is supported by behavioural data. For example, concordance between binding to the transporter and changes in locomotor activity has been demonstrated for a large series of cocaine analogues. The dopamine hypothesis suggests possible pharmacotherapeutic strategies to combat psychostimulant use, and these approaches, including available human data and future directions of pharmacological treatments are discussed in this paper. The limitations of the dopamine hypothesis with respect to psychostimulant dependence and abuse liability are also summarized, to provide a broad perspective of the current status of this hypothesis.