Both A2A and Gpr6 are positively coupled to Gs/Golf proteins, implicating their role in antagonizing the D2-receptor in D2+ MSNs. Indeed, stimulation of A2A receptors has been shown to reduce both the development and expression of cocaine sensitization (Filip et al., 2006), impair the initiation of cocaine self-administration (Knapp et al., 2001), and antagonize the reinstatement of cocaine seeking elicited by cocaine, D2-receptor stimulation, or cocaine-conditioned cues (Bachtell and Self, 2009). As Gpr6 is also enriched in D2+ MSNs (Lobo et al., 2007), its role in behavioral functions of the striatum should be evaluated. To date, it has been shown to influence instrumental learning (Lobo et al., 2007) but its role in drug abuse models is yet unknown.
