The comparatively poor skill of D2R-/- mice during discrimination trials suggests a role for D2Rs in acquisition of appropriate S+/S- relationships in operant associative learning. Several studies have demonstrated that both the acquisition [6,7] and expression [9] of associative learning are mediated by dopamine D1Rs. Most literature reviews identify dopamine D1Rs with dopamine-mediated learning and D2Rs with motor related behaviors [e.g. [24]]. Moreover, it has been reported that acute administration of the dopamine D2/3 antagonist, raclopride, actually improves acquisition of food-motivated associative learning [6]. However, only acute administrations of antagonists were given, and learning was not measured during complete D1R or D2R blockade [6]. Significantly, the reports cited above failed to address the technical limitations of the approach: i.e. that the antagonists used lack adequate subtype specificity and only partially blocked D2R-mediated signaling thus making it impossible to rigorously assess the role of D2R-mediated signaling in associative and reversal learning. Additionally, none of these studies addressed the observation that the effects of D2R antagonists on locomotion and learning depend on whether exposure is chronic or acute [e.g. [15,16]].