The effects of dopamine D(1) receptor blockade in the prelimbic-infralimbic areas on behavioral flexibility

This study examined the effects of a dopamine D(1) antagonist, SCH23390, infused into the prelimbic-infralimbic areas on the acquisition of a response and visual-cue discrimination task, as well as a shift from a response to a visual-cue discrimination and vice versa. Each test was carried out in a cross-maze. The response discrimination required learning to always turn in the same direction (right or left) for a cereal reinforcement. The visual-cue discrimination required learning to always enter the arm with the visual cue. In experiment 1, rats were tested on the response discrimination task, followed by the visual-cue discrimination task. In experiment 2, the testing order was reversed. Bilateral infusions of SCH23390 (0.1 or 1 microg/0.5 microL) into the prelimbic-infralimbic areas did not impair acquisition of the response or visual-cue discrimination tasks. SCH23390 injections at 1 microg, but not 0.1 microg impaired performance when shifting from a response to a visual-cue discrimination, and vice versa. Analysis of the errors revealed that the deficit was due to perseveration of the previously learned strategy. These results suggest that activation of dopamine D(1) receptors in the prelimbic-infralimbic areas may be critical for the suppression of a previously relevant strategy and/or generating new strategies.