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Cerebral Cortex Advance Access published online on November 10, 2004
Cerebral Cortex, doi:10.1093/cercor/bhh202
© 2004 by Oxford University Press
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Article

Mice Lacking Dopamine D2 and D3 Receptors Exhibit Differential Activation of Prefrontal Cortical Neurons during Tasks Requiring Attention

Sara B. Glickstein 1, Deirdre A. DeSteno 2, Patrick R. Hof 3, and Claudia Schmauss 4*

1 Department of Neuroscience, New York State Psychiatric Institute, New York, USA
2 Department of Pharmacology, Columbia University, New York, NY 10032, USA
3 Department of Neuroscience, Mount Sinai School of Medicine, New York, NY 10029, USA
4 Department of Neuroscience, New York State Psychiatric Institute, New York, USA; Department of Psychiatry, Columbia University, New York, NY 10032, USA

* To whom correspondence should be addressed.
Claudia Schmauss, E-mail: schmauss{at}neuron.cpmc.columbia.edu


  Abstract

Mice lacking dopamine D2 and D3 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. D2 mutants exhibited significant impairment in the first compound discrimination, indicating deficits in the initial acquisition of the task-governing rules. In contrast, D3 mutants performed significantly better in a set-shifting phase that required reversal learning. The higher response accuracy of D3 mutants was also accompanied by significantly increased response latency. A stereological assessment of test-induced expression of the c-fos gene in neurons of the anterior cingulate and prelimbic/infralimbic cortices revealed highest activation in D3 mutants, intermediate activation in wildtype and lowest activation in D2 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 D2-like receptor that is activated.

Keywords: anterior cingulate cortex; cognitive control; dopamine; immunocytochemistry; infralimbic cortex; prelimbic cortex.
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