The behavioral role of individual ACh receptor subtypes in NAc is more complex, however. Consistent with a role for the pause in NAc cholinergic neurons in behaviors related to drug reward, antagonism of α7-type nAChRs in NAc increases motivation to lever press for nicotine (Brunzell and McIntosh, 2012). Less intuitively, blockade of mAChRs using scopolamine decreases reinstatement of cocaine seeking (Yee et al., 2011), but this may be due to increased ACh release through blockade of inhibitory autoreceptors (Douglas et al., 2001). Since neuromodulation can be complex, it has also been shown that antagonism of the α6/β2 class of nAChRs expressed on DA terminals in NAc decreases the breakpoint for progressive ratio responding in rats self-administering nicotine, suggesting that there is also a role for ACh signaling through this class of receptors for mediating the motivational value of nicotine (Brunzell et al., 2010).
