Finally, recent literature reveals that the two MSNs exert antagonistic effects in drug-related behaviors, where activation of D1+ MSNs or inhibition of D2+ MSNs enhances an animal’s sensitivity to a drug of abuse (Hikida et al., 2010; Lobo et al., 2010; Ferguson et al., 2011). These findings are consistent with opposing roles of the two MSNs and their direct vs. indirect pathways in the basal ganglia in motor behaviors (Alexander et al., 1986; Albin et al., 1989; Graybiel, 2000; Kravitz et al., 2010). This recent literature is in accord with the general idea that dopaminergic neurotransmission, which is activated by all drugs of abuse, facilitates glutamatergic activation of D1+ MSNs while inhibiting glutamatergic activation of D2+ MSNs through its actions on D1 vs. D2 dopamine receptors (Figure 1). In this review, we address the current knowledge of the distinct molecular signaling exhibited by these two MSN subtypes in relation to their functional roles and responses to drugs of abuse.
