Modulation of cue‐triggered reward seeking by cholinergic signaling in the dorsomedial striatum

The dorsomedial striatum ( DMS ) has been strongly implicated in flexible, outcome‐based decision making, including the outcome‐specific Pavlovian‐to‐instrumental transfer effect ( PIT ), which measures the tendency for a reward‐predictive cue to preferentially motivate actions that have been associated with the predicted reward over actions associated with different rewards. Although the neurochemical underpinnings of this effect are not well understood, there is growing evidence that striatal acetylcholine signaling may play an important role. This study investigated this hypothesis by assessing the effects of intra‐ DMS infusions of the nicotinic antagonist mecamylamine or the muscarinic antagonist scopolamine on expression of specific PIT in rats. These treatments produced dissociable behavioral effects. Mecamylamine infusions enhanced rats’ tendency to use specific cue‐elicited outcome expectations to select whichever action was trained with the predicted outcome, relative to their performance when tested after vehicle infusions. In contrast, scopolamine infusions appeared to render instrumental performance insensitive to this motivational influence of reward‐paired cues. These drug treatments had no detectable effect on conditioned food cup approach behavior, indicating that they selectively perturbed cue‐guided action selection without producing more wide‐ranging alterations in behavioral control. Our findings reveal an important role for DMS acetylcholine signaling in modulating the impact of cue‐evoked reward expectations on instrumental action selection.