Although synaptic adaptations were not examined, a study worth mentioning directly tested the behavioral roles of NAc indirect and direct pathway MSNs (Lobo et al., 2010). Optogenetic activation of D1 receptor-expressing direct pathway NAc MSNs dramatically enhanced the rewarding effects of a threshold dose of cocaine in a conditioned place preference protocol whereas activation of D2 receptor-expressing indirect pathway NAc MSNs dramatically attenuated cocaine reward. Other molecular manipulations of direct versus indirect pathway MSNs in the striatum also support the hypothesis that the specific circuits in which these two subpopulations of MSNs participate have profoundly different behavioral roles in addiction related behaviors (Hikida et al., 2010; Bateup et al., 2010).
