Rat Prefrontal Dopamine and Cognitive Control: Impaired and Enhanced Conflict Performance

It has been proposed that the cognitive dysfunction observed in patients with schizophrenia reflects a failure in cognitive control, in particular an inability to use task-relevant information to guide behavior. Using a prefrontal-dependent task designed to reflect aspects of cue and response conflict seen in human cognitive paradigms, we examined the influence of prefrontal dopamine receptor manipulation on the contextual control of response conflict. Rats were trained on two biconditional discrimination tasks, one auditory and one visual, in two discriminably different contexts. At test, audiovisual compounds of these training stimuli were presented, in extinction, in each of the training contexts. These compounds were formed in such a way that the individual elements previously dictated different responses during training, termed incongruent trials. Studies have shown that rats use contextual information to disambiguate the conflicting information provided by incongruent compounds, responding in manner that is appropriate to the stimulus element that was trained in the test context. Direct infusion of the D1 receptor agonist SKF-38393 into the prelimbic cortex was found to modulate incongruent trial performance in a manner that was dependent upon baseline performance: animals in the low baseline group demonstrated improved incongruent performance following infusion of SKF-38393 into the prelimbic cortex. In contrast, high performers showed a reduction in accuracy during incongruent compounds. This paradigm provides a reliable framework for assessing the efficacy of preclinical agents in treating the cognitive impairments seen in frontal-related disorders such as schizophrenia.