The Effects of Dopamine D₁ Receptor Blockade in the Prelimbic–Infralimbic Areas on Behavioral Flexibility

Abstract

This study examined the effects of a dopamine D₁antagonist, 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 μg/0.5 μL) into the prelimbic–infralimbic areas did not impair acquisition of the response or visual-cue discrimination tasks. SCH23390 injections at 1 μg, but not 0.1 μg 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 D₁ receptors in the prelimbic–infralimbic areas may be critical for the suppression of a previously relevant strategy and/or generating new strategies.