prefrontal cortex are unaffected in DAT KO mice (Shen, et al., 2004) or which is consistent with NET being the primary mediator of dopamine uptake in the prefrontal cortex (Mazei, Pluto, Kirkbride, & Pehek, 2002). One of the results of this circumstance would therefore be that the ratio of cortical to subcortical dopaminergic activity is altered in DAT KO mice, so that DAT KO mice are essentially hypofrontal. Indeed, deficits in prepulse inhibition of startle in DAT KO mice (Barr, et al., 2004; Ralph, Paulus, Fumagalli, Caron, & Geyer, 2001; Yamashita, et al., 2006) can be reversed by administration of NET blockers in the prefrontal cortex (Arime, Kasahara, Hall, Uhl, & Sora, 2012), which elevate dopaminergic tone and is associated with activation of prefrontocortical glutamatergic projections to the nucleus accumbens. Consistent with this hypothesis, a recent brain imaging study demonstrated reduced activity of an apparent corticostriatal circuit in DAT KO mice (X. Zhang, et al., 2010).
