by Cdk5, which inhibits PKA signaling, selectively in D2+ MSNs (Bateup et al., 2008). Finally this group showed that deletion of DARPP-32 from each MSN subtype using D1-Cre and D2-Cre BAC transgenic mice results in opposite regulation of cocaine-induced locomotor activity (Bateup et al., 2010). Loss of DARPP-32 from D1+ MSNs diminished the locomotor effects of cocaine, which mimics previous data evaluating a total DARPP-32 knockout (Fienberg et al., 1998), whereas loss of DARPP-32 from D2+ MSNs enhanced cocaine locomotor responses. Such data provide concrete evidence for differential roles of DARPP-32 in the two MSNs in response to drugs of abuse and illustrate the importance of cell-type-specific methods to fully understand the contribution of these two neuronal types in drug addiction.
