The role of dopamine receptors in drug abuse is complex and often elusive (Self, 2010). There is an abundance of literature on the role of D1 and D2-receptor agonists and antagonists in modulating rewarding properties and self-administration of drugs of abuse, however, the results differ depending on the type of agonist/antagonist used, the type of delivery (systemic vs. brain region-specific), and the timing of the treatment (Self, 2010). Such results are further confounded by non-striatal specific effects, such as the contribution of pre-synaptic D2-receptors from the VTA or presence of D1 receptors in many other limbic regions, and the lack of specificity of the agonists/antagonists utilized as well as the expression of D1-like and D2-like receptors in both MSN subtypes as noted earlier. In general, it is thought that D1 receptors play a more predominant role in the primary rewarding properties of drugs of abuse, whereas D2-receptors play a role in drug seeking mechanisms (Self et al., 1996; Self, 2010). Studies with D1 receptor and D2-receptor knockout mice provide some insight into the role of these receptors in the two
