Because cocaine can increase the level of serotonin in the synapse by blocking reuptake via the serotonin transporter [Cami and Farre, 2003], genetic variants involved in the serotonergic system are candidates for CD risk [Saxon et al., 2005]. The 5-HT2C receptor, encoded by HTR2C, modulates the discriminative stimulus effects of cocaine [Callahan and Cunningham, 1995; Frankel and Cunningham, 2004]. Our finding of an association of HTR2C with both DSM-IV CD and one of the two subtypes we examined is, to our knowledge, the first report of such an association. The finding is consistent with the pharmacology of cocaine and, if replicated, points to differences in the pathophysiology of CD and AD, as studies of HTR2C have failed to show an association with AD [Herman and Balogh, 2012].
