Sora and Uhl, unpublished observation).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 of fluoxetine or the NET blocker reboxetine increased dopamine release in the nucleus accumbens of DAT KO mice, but not in WT mice (Carboni, et al., 2001; Shen, et al., 2004). These findings suggest that cocaine is rewarding in DAT KO mice because of actions at SERT (and perhaps NET). This might be considered to be consistent with an “occult” reuptake hypothesis (Y. J. Liu & Edwards, 1997; G. R. Uhl, et al., 2000), whereby cocaine continues to produce rewarding effects in DAT KO mice by elevating dopamine levels in the striatum, but by actions at SERT and NET rather than DAT. However, this does not appear to be the case as administration of cocaine, fluoxetine or nisoxetine into the striatum fail to affect dopamine levels or alter dopamine clearance in DAT KO mice (Budygin, John, Mateo, & Jones, 2002; Mateo, Budygin, John, Banks, & Jones, 2004; Mateo, Budygin, John, & Jones, 2004; Shen, et al., 2004). By contrast, local
