Dose-dependent effects of prefrontal dopamine on behavioral state in rats.

An inverted-U mechanism has been proposed to explain findings that both under- and overstimulation of dopamine (DA) receptors in medial prefrontal cortex (mPFC) result in working memory impairments. Dopamine release in the mPFC is also associated with the mediation of other behavioral processes such as affective regulation, reward, and nociception. The present studies investigated mPFC DA dose-dependent effects on the performance of tasks that tap these other processes, including delayed alternation in the T maze for working memory, a water maze task for escape, the elevated plus maze for anxiolytic/anxiogenic effects, place preference conditioning for reward effects, the tail flick test for nociception, and a measure of locomotor activity for general arousal. Injection of 5 μg of DA improved working memory, was anxiolytic in the plus maze, and increased pain sensitivity, but did not have any effects on water maze escape, place preference or locomotor activity. Doses of 10 μg and 20 μg impaired working memory and substantially decreased pain sensitivity, but did not affect plus maze behavior or locomotor activity. The 20-μg dose also enhanced water maze escape. Taken together, these findings suggest a profile of two distinct behavioral states induced by low or high levels of mPFC DA: a low level facilitates foraging functions such as working memory and exploratory behaviors, with increased pain sensitivity, while higher levels facilitate stress-related adaptations, such as escape from threat and reduced pain sensitivity. These findings are concordant with behavioral flexibility views of mPFC DA functions.