Inactivation of dorsolateral striatum enhances sensitivity to changes in the action-outcome contingency in instrumental conditioning.

Actions become compulsive when they are no longer controlled by their consequences. Compulsivity can be assessed using the omission procedure in which animals are required to withhold a previously reinforced action to earn reward. The current study tested the hypothesis that inactivation of the dorsolateral striatum (DLS), a structure implicated in habitual behavior, can enhance sensitivity to changes in the action-outcome contingency during omission training, thus leading to a reduction in compulsive responding. Over 10 days rats were trained to press a freely available lever for sucrose reward delivered on interval schedules of reinforcement. After learning to press the lever at a stable and high rate, rats in the omission group received a session in which the rewards were now delayed by pressing the lever; i.e. withholding lever pressing resulted in increased access to reward. A control group was yoked to the omission group and received the same number and pattern of reward delivery but without the omission contingency. Half the rats in each group received infusions of vehicle into the DLS prior to this training whereas the remainder received an infusion of the GABA-A receptor agonist muscimol. On the next day, the effect of these treatments was assessed on a probe test in which the tendency of the various groups to press the lever was assessed in extinction and without drug infusion. Rats that received vehicle infusions prior to the omission session showed complete insensitivity to the newly imposed omission contingency. In contrast, rats given the infusion of muscimol selectively reduced lever pressing compared to yoked controls. Thus, extended training with interval schedules resulted in compulsive lever pressing that prevented the learning of the omission contingency, whereas inactivation of the DLS appeared to enhance the rats' sensitivity to this change in the action-outcome contingency.