sensitization, our results do not eliminate roles for NMDARs in other functions of these DA neurons. Indeed, we also demonstrate a loss of NMDAR-mediated synaptic plasticity in these DA neurons, as well as changes in DA neurotransmission in the NAc of NR1DATCre animals. It has been proposed that the acquisition of conditioned behavioral responses is governed by the phasic firing of DA neurons initiated by NMDAR activity [21,31,32,33,34]. The increased DA release elicited by single-pulse electrical stimulation that we observed is consistent with the modest elevation in basal DA levels in similar NR1-lacking mice [10]. However, DA release at higher burst-like frequencies of axon terminal activation was reduced in the NAc of mice lacking NR1 in DA neurons. This is consistent with a previous report of reduced burst-induced DA release in other NMDAR KO mice [21]. Previous studies using in vivo electrochemical techniques have also shown that higher frequency DA transients are associated with DA neuron bursting, and occur in the NAc when animals explore a novel environment [35]. Therefore, the diminished burst-stimu- lation-induced DA release in the NAc that we observed may explain the significantly reduced locomotor responses of NR1DATCre mice when exposed to a novel environment. Thus, we speculate that the blunted response to novel environment may be mediated by a deficit in burst-related DA release. Although this, and the other changes we observed in NAc DA release in the NR1 KO animals appear to directly implicate NMDARs, we also found that these changes did not occur during acute NMDAR antagonist application in WT mice. This implies that there are alterations in DAergic circuits that are secondary to the absence of NR1, and that these compensatory changes should be considered when References 1. 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