2007). Such data support important roles for D1 and D2-receptors in the two MSNs in multiple aspects of drug abuse, however, the knockouts lack striatal specificity and occur early in development, thus one cannot rule out other brain regions and cell-types and developmental factors in mediating these behaviors. Finally, decreased levels of D2/D3 receptors in striatum, as visualized by brain imaging, has become a common marker of addiction in human patients especially during periods of withdrawal (Volkow et al., 2009). Rodents receiving viral-mediated gene transfer of D2-receptors to the NAc display attenuated cocaine self-administration and ethanol consumption (Thanos et al., 2004, 2008). These studies were not performed in a cell-type-specific manner, so we cannot rule out the possible effect of D2-receptor overexpression influencing D1+ MSNs. This collection of data emphasizes the need to move to more selective approaches, including cell-type-specific, region-specific, and even temporally specific manipulations of the dopamine receptors to better elucidate their functional roles in the two MSN subtypes in drug addiction.
