Behavioral functions of dopamine in the anterior cingulate cortex.

摘要

The dopaminergic (DA) innervation of the rat medial frontal cortex (mFC) has received recent attention for its role in mediating working memory functions. An inverted U mechanism has been proposed to explain findings that both under- and over-stimulation of mFC DA receptors result in working memory impairments. However, the mFC and DA functionality have also been tied to the mediation of other behaviors such as affective regulation, reward, nociception, and responses to stressors, none of which contain a working memory component. The current series of studies was designed to explore the possibility that the inverted U function of mFC DA could also differentially affect the performance of tasks chosen to tap these other aspects of behavior. The chosen tasks were delayed alternation in the T maze for working memory, the Morris water maze task for escape responding, the elevated plus maze for anxiolytic/anxiogenic effects, place preference conditioning for reward effects, the tail flick test to assay changes in pain sensitivity, and a measure of locomotor activity in a habituated environment. Doses of DA HCl (5, 10, and 20 μg in 1 μl saline) were microinjected into the mFC of rats and task performance changes were recorded. The dose of DA 5 significantly improved delayed alternation response accuracy, was mildly anxiolytic in the plus maze, and significantly increased pain sensitivity, but did not have any effects on water maze escape, or hedonic or locomotor effects. The doses of DA 10 and DA 20 impaired delayed alternation and substantially decreased pain sensitivity, but did not affect plus maze behavior or locomotor activity. The DA 20 dose also enhanced water maze escape and did not have hedonic effects. Taken together, these findings suggest a profile of two very different behavioral states induced by the different levels of mFC DA: the low level appears to facilitate attentional processes such as working memory and exploratory behaviors and to increase pain sensitivity, while the higher levels appear to facilitate stress-coping behaviors such as aiding escape from potential threat and reducing pain sensitivity. These findings are concordant with response selection/behavioral flexibility views of mFC and DA functions.