These adaptations in DAT KO mice could be considered from a couple of different perspectives. On the one hand they might be interpreted as being uninformative as regards the usual mechanisms that underlie the rewarding effects of cocaine. In this respect it is important to note that a transgenic line was created in which DAT maintains much of its normal uptake function, but is insensitive to cocaine, the DAT-CI transgenic line (R. Chen, et al., 2006). These mice show neither cocaine-induced elevation of dopamine levels in the nucleus accumbens nor cocaine conditioned place preference. Although this line clearly demonstrates that elimination of DAT as a target for cocaine can have profound effects on cocaine reward, the DAT KO mouse does demonstrate that under some circumstances other mechanisms may mediate the rewarding effects of cocaine. Indeed, in dopamine deficient mice in which transgenic manipulations produce an almost complete elimination of dopamine (Zhou & Palmiter, 1995), cocaine continues to produce rewarding effects that are also serotonin-mediated (Hnasko, Sotak, & Palmiter, 2007).
