More selective genetic manipulations, however, call this interpretation into question. Specifically, conditionally deleting the NMDAR subunit NR1 selectively in DA neurons of adult mice caused a loss of NMDAR EPSCs as well as the cocaine-evoked synaptic plasticity yet behavioral sensitization and CPP were still normal (Engblom et al., 2008). A behavioral repercussion of this genetic manipulation became apparent only during the withdrawal period following drug self-administration, a time period during which the normal reinstatement of self-administration triggered by a priming dose of cocaine was abolished or when cue-induced cocaine seeking after more than a month of withdrawal was significantly reduced (Mameli et al., 2009). The postnatal, rather than constitutive, deletion of NR1 from DA neurons may explain an apparent difference with another study in which mice with a constitutive removal of functional NMDARs from DA neurons exhibited impaired CPP (Zweifel et al., 2008). In these mice the absence of NMDARs during development led to an increase/decrease in AMPAR EPSCs, presumably due to a form of synaptic scaling (Adesnik et al., 2008). Interestingly in the same DATCre-NR1 mouse behavioral sensitization was
