Mice lacking dopamine D 2 and D 3 receptors and wildtype littermates were tested in a two-choice perceptual discrimination test that is dependent upon optimal functioning of the prefrontal cortex. Both mutants showed no deficits in attending to the perceptual stimuli or in shifting attention between stimulus dimensions. However, the performance of both mutants differed from the wildtype in different test phases. D 2 mutants exhibited significant impairment in the first compound discrimination,

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... ndicating deficits in the initial acquisition of the task-governing rules. In contrast, D 3 mutants performed significantly better in a setshifting phase that required reversal learning. The higher response accuracy of D 3 mutants was also accompanied by significantly increased response latency. A stereological assessment of testinduced expression of the c-fos gene in neurons of the anterior cingulate and prelimbic/infralimbic cortices revealed highest activation in D 3 mutants, intermediate activation in wildtype and lowest activation in D 2 mutants, indicating that response accuracy in the cognitive test correlates with the magnitude of prefrontal cortical activation regardless of which test phases revealed different performances. The study illustrates that dopamine differentially modulates prefrontal cortical activity during tasks requiring attention depending upon the type of D 2 -like receptor that is activated.