In any case the ability of cocaine to have any rewarding effects at all in these mice suggests that some other mechanisms must be involved, and several potential possibilities were suggested, including mediation by one of the other two main targets of cocaine. Although deletion of either SERT or NET was shown to increase cocaine conditioned place preference (Sora, et al., 1998; F. Xu, et al., 2000), perhaps due to elimination of aversive effects of cocaine (G. R. Uhl, et al., 2002), one possibility was that, in the absence of DAT, the additional deletion of SERT or NET would eliminate the rewarding effects of cocaine. Combined deletion of DAT and SERT was found to eliminate the rewarding effects of cocaine in the conditioned place preference paradigm (Sora, Hall, et al., 2001). Combined deletion of NET and DAT was lethal (Hall, Sora and Uhl, unpublished observation). Furthermore, the selective SERT and NET blockers fluoxetine and nisoxetine were shown to have rewarding effects in DAT KO mice that they did not have in WT mice (Hall, et al., 2002), while peripheral administration
