The effects of repeated stressful experiences (10 min restraint, daily) on the levels of dopamine and metabolites in the nucleus accumbens septi and frontal cortex were evaluated. In naive mice, restraint stress increased 3-4-dihydroxyphenylacetic acid, homovanillic acid, and 3-methoxytyramine levels in the nucleus accumbens and 3-4-dihydroxyphenylacetic acid levels in the frontal cortex. The effects of stress on 3-methoxytyramine and homovanillic acid levels in the nucleus accumbens septi disappeared within five days of daily restraint experiences and the increase in 3-4-dihydroxyphenylacetic acid levels was no longer evident by the 10th day. By contrast, the response of mesocortical dopamine system to restraint (increased 3-4-dihydroxyphenylacetic acid levels) was unaffected by either five or 10 days of exposure to the stressor. Moreover, 10 min of restraint were still able to increase 3-4-dihydroxyphenylacetic acid levels in the frontal cortex of mice repeatedly exposed (nine days) to 120 min restraint. These results indicate that the mesolimbic and the mesocortical dopamine systems adapt differently to repeated exposure to a stressor.