Medium spiny neurons receive glutamatergic input from multiple brain regions including prefrontal cortex, amygdala, and hippocampus, and GABAergic input from local interneurons and perhaps collateral inputs from other MSNs. Net excitatory and inhibitory regulation of MSNs is no doubt crucial in regulating the drug-addicted state, and there is now a growing literature on the complex ways in which drugs of abuse alter glutamatergic neurotransmission in particular in the NAc (Pierce et al., 1996; Thomas et al., 2001; Beurrier and Malenka, 2002; Kourrich et al., 2007; Bachtell and Self, 2008; Bachtell et al., 2008; Conrad et al., 2008; Kalivas, 2009; Wolf, 2010). Although MSNs are thought to primarily exist in an inhibited down-state under basal conditions with glutamate driving activity of both cell-types, there remains limited information with respect to distinct regulation occurring in D1 vs. D2 MSNs.
