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In recent years, gene knock-out studies have greatly expanded understanding of the molecular basis of drug reward and drug addiction. One of the consequences of these studies has been to produce a more pluralistic view of the underlying neurochemical mechanisms that mediate drug reward after the development of a strongly dopamine-centered view in the 1980s. This is not to say that dopamine does not have a central role in drug reward and drug addiction, but rather a fuller examination of these mechanisms involves the complex neurocircuitry of which dopamine systems are a part. This view is not new, but has been expressed from a variety of perspectives. Gene knock-out studies have indicated a particular approach to examining the nature of interactions between different parts of this circuitry. This chapter will focus on the role of serotonin, and in particular the serotonin transporter (SERT), in drug reward. This more pluralistic perspective became apparent in gene knock-out studies of the rewarding effects of drugs of abuse which demonstrated that deletion of the dopamine transporter (DAT) did not eliminate the rewarding effects of cocaine, and subsequent findings that implicated a critical role of SERT in a variety of circumstances. These studies also validated the central role of dopamine in drug reward, and consequently the role of SERT must be considered largely from the point of view of interactions with dopamine systems.
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