Title:

The Cognitive Effects of Dopaminergic Lesions to Anterior Cingulate Cortex in Rats

Dysfunction in the anterior cingulate cortex (ACC) has been implicated in many neuropsychiatric disorders such as, but not limited to, attention deficit hyperactivity disorder, addiction, and schizophrenia. Dopaminergic projections to the ACC are hypothesized to be critical to error processing, timing of responses and filtering irrelevant information. In previous work, rats with excitotoxic lesions to the ACC showed an increased susceptibility to distraction when a complex stimulus contained an attribute previously paired with reinforcement, but, were not more distractible than sham lesioned subjects when presented with irrelevant stimuli that did not have a reinforcement history. The current study is aimed at identifying the neurochemical basis of these effects. Rats infused with a selective dopaminergic toxin or it’s vehicle into the ACC were assessed in two attentional tasks, an attentional set shifting task (ASST), and a sustained attention task (SAT). The ASST measures the ability of subjects to form and shift an attentional set in the presence of irrelevant cues that have previously been paired with reinforcement. The SAT includes tests of distractors never predictive of reinforcement, changes in timing of events as well as timing between responses and reinforcement. Both male and female dopaminergic lesioned subjects were more susceptible to distraction and impaired when reinforcement contingencies were reversed in the ASST. Dopamine lesioned rats were not susceptible to distraction when irrelevant stimuli had no prior reinforcement history. Dopaminergic lesions impaired, but did not abolish, the ability of subjects to adapt when the timing of responses and reinforcement was changed. Female, but not male, lesioned rats were impaired when the event rate was made more temporally unpredictable. Together these data show that DA in the ACC is involved in filtering salient stimuli and updating responding when reinforcement contingencies are altered.

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