Neuronal circuitry underlying the impact of D3 receptor ligands in drug addiction

Since the cloning of the D3 receptor in the early 1990s, there has been a great deal of interest in this receptor as a possible therapeutic target for drug addiction. The development of a D3 ligand suitable for use in humans has remained elusive, so the study of the function of the D3 receptor and its possible therapeutic efficacy has largely been restricted to animals. Pre-clinical studies have established that systemic administration of D3 ligands, particularly antagonists and partial agonists, can alter drug-seeking in animals. Despite over a decade of research, few studies have investigated the effects of intra-cerebral infusion of D3 ligands on drug-seeking. In the present review, these studies are summarized, which have largely focused on stimulus-controlled behaviors. Converging evidence from studies of D3 receptor expression, Fos and pharmacological Magnetic Resonance Imaging (phMRI) is also provided to delineate some of the D3 brain systems involved in drug-seeking and taking. The data so far indicate that different brain systems may be involved in different types of stimulus control as well as drug taking.