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 NR1 subunit in D1+ MSNs attenuates amphetamine sensitization and this phenotype was rescued by resupplying the NR1 subunit to D1+ MSNs specifically in the NAc (Beutler et al., 2011). Finally, knockdown of the mGluR5 subunit, using RNA interference, in D1+ MSNs has no effect on the initial rewarding properties of cocaine but diminishes the cue-induced reinstatement of cocaine seeking (Novak et al., 2010). While these data reveal compelling roles for glutamatergic signaling in D1+ MSNs, future work is needed to study glutamatergic systems in D2+ MSNs. Future research should also evaluate how modulation of these glutamate receptor subunits in the two MSN subtypes affects the structural synaptic changes observed in NAc after drugs of abuse (Dietz et al., 2009; Russo et al., 2010), particularly the dendritic alterations observed after cocaine exposure selectively in the D1+ MSNs (Lee et al., 2006; Kim et al., 2011) which may be associated with the increase in miniature excitatory postsynaptic currents observed in D1+ MSNs
