Because of the interactions between DAT and VMAT2 in determining the dynamics of dopamine release, the interactive effects of heterozygous (+/−) deletion of the two genes was recently examined on methamphetamine locomotion and sensitization of locomotion (Fukushima, et al., 2007). As might be expected from previous studies with amphetamine (Spielewoy, et al., 2001; Takahashi, et al., 1997), the acute locomotor stimulant effects of methamphetamine were increased in VMAT2 +/− mice and decreased in DAT +/− mice. Similarly, sensitization of these effects was also increased inVMAT2 +/− mice and reduced in DAT +/− mice, in contrast to a previous study using amphetamine (Y. M. Wang, et al., 1997). It might be noted that the initial response of VMAT2 +/− mice was so high that there may have been ceiling effects. No interactive effects were observed in the Fukushima et al. (2007) study between the two genetic manipulations. The identification of effects in heterozygous mice may make it more likely that genetic differences in humans that alter gene expression by similar magnitudes might have observable effects on sensitivity to amphetamine-like drugs.
