Optimal working memory functions within a narrow range of dopamine neurotransmission (i.e. the classic inverted U-shaped curve) regulated by the G protein-coupled family of dopamine receptors (Williams & Castner, 2006). Dopamine D1 receptors are known to modulate the persistent neuronal activity that is needed to continuously update information in working memory (Paspalas & Goldman-Rakic, 2005). Dopamine D2 receptors also modulate components of working memory (Wang, Vijayraghavan & Goldman-Rakic, 2004), although to a lesser extent than D1 receptors (McNab, Varrone, Farde, Jucaite, Bystritsky, Forssberg & Klingberg, 2009). It is thus important to know the degree to which genetic variation influences the differential roles that D1 and D2 receptors play in working memory. A functional dopamine D1 receptor gene (DRD1) polymorphism (rs686) that affects D1 expression has been identified (Huang, Ma, Payne, Beuten, Dupont & Li, 2008), as have three functional dopamine D2 receptor gene (DRD2) polymorphisms (rs12364283, rs2283265 and rs1076560) (Zhang, Bertolino, Fazio, Blasi, Rampino, Romano, Lee, Xiao, Papp, Wang & Sadée, 2007). However, only the DRD2 variants have at this point been associated with working memory (Zhang et al., 2007).
