This raises the possibility that the GPR52 activation improves positive symptoms of schizophrenia by antagonizing the Gi/o-coupled D2 receptor activity in striatopallidal MSNs and improves schizophrenic negative symptoms and cognitive impairment through enhancement of the NMDA receptor activity via protein kinase A (PKA) in prefrontal cortical neurons, as seen in D1 receptor-NMDA signal transduction (Figure 2) [62,63,64]. The gene discussed is GPR52; the disease is schizophrenia.