Dopamine regulates emotional and motivational behavior through the mesolimbic dopaminergic pathway. Dopamine D2 receptors have two specific isoforms, D2S and D2L, and participate in presynaptic and postsynaptic dopaminergic transmission in the direct pathway of basal ganglia network, respectively. Previously, we demonstrated that D2L receptors in the indirect pathway of nucleus accumbens play an important role in aversive learning (Hikida et al. 2013). Here we performed cognitive task to test whether D2L receptors could be involved in cognitive learning by using D2L knockout mice (D2L KO mice). In the visual discrimination (VD) task, D2L KO mice exhibited significant lower accuracy than wild-type mice. D2L KO mice also showed low accuracy in the reversal VD task. These results indicate that D2L receptors may be critical to cognitive learning. Next, to define molecular changes of D2L KO mice, we examined various mRNA expression levels of various downstream factors in D2 signaling. Phosphodiesterases (PDEs), enzymes facilitate hydrolysis of the second messenger molecules cAMP and cGMP, are one of crucial factors of D2 signaling in the indirect pathway of basal ganglia. In the nucleus accumbens and striatum of D2L KO mice, we identified changes in mRNA expression levels of PDEs in an isoform specific manner. These results suggest that D2L receptors and its signaling have a critical role in cognitive learning.