In this regard, NAc A2AR KD selectively improving cognitive flexibility, combined with the noted safety profile of A2AR antagonists and caffeine in clinical phase III trials for motor benefits in Parkinson’s disease (Chase et al., 2003) suggests that pharmacological targeting striatal A2AR may represent a novel treatment strategy for the deficits of cognitive flexibility in various neuropsychiatric disorders. The gene discussed is ADORA2A; the disease is Parkinson disease.