ΔFosB overexpression in D1+ MSNs (see below for more details) enhances the rewarding effects of cocaine and increases levels of the Ca2+-impermeable glutamate receptor subunit, GluR2, in NAc. Furthermore, viral-mediated gene transfer of GluR2 to the NAc similarly enhances the rewarding effects of cocaine (Kelz et al., 1999). However, it is not known whether the induction of GluR2 seen in response to ΔFosB overexpression in D1+ MSNs is also specific to these neurons, and the viral overexpression of GluR2 is not cell-type-specific, therefore we cannot infer direct conclusions about GluR2 function in these two MSNs in drug reward. Heusner and Palmiter (2005) assessed the role of NMDA glutamatergic conductance in cocaine behaviors by expressing an NR1 subunit, which contains a mutation in the pore that reduces calcium flux, selectively in D1+ MSNs. This group showed that lack of NMDA conductance in D1+ MSNs prevents cocaine-induced CPP and cocaine locomotor sensitization, highlighting the necessity for NMDA signaling in D1+ MSNs for the rewarding and sensitizing effects of cocaine (Heusner and Palmiter, 2005). Furthermore, recently it was found that knocking out the
