We investigated the effects of two types of psychological stress, novelty stress and psychological stress using the communication box, on dopamine and serotonin systems in subregions of the frontal cortex and nucleus accumbens of rats. Placement of rats into a compartment of the communication box (novelty stress) increased both dopamine and serotonin metabolism in medial precentral, anterior cingulate, and prelimbic subregions of the frontal cortex as evaluated by the levels of 3,4-dihydroxyphenylacetic acid and homovanillic acid for dopamine, and 5-hydroxyindoleacetic acid for serotonin. In contrast, novelty stress had no effect on these monoamine systems in infralimbic and sulcal subregions of the frontal cortex. In the nucleus accumbens, novelty stress increased both dopamine and serotonin metabolism in the shell, but decreased dopamine metabolism in the core. On the other hand, psychological stress using the communication box augmented dopamine metabolism in the anterior cingulate and prelimbic subregions. This stress, however, failed to affect the dopamine system in the medial precentral, infralimbic and sulcal subregions. In the nucleus accumbens, the stress selectively decreased dopamine metabolism in the shell but showed no effect in the core. The serotonin system showed little change due to the stress. These results demonstrate that psychological stress causes distinct changes in both the dopamine and serotonin systems in the frontal cortex and the nucleus accumbens. These changes vary with the subregions of these areas, suggesting that the region-specific responsiveness to psychological stress reflects the functional differences among these subregions. In addition, our results also suggest that changes in brain monoamine systems induced by psychological stress are quite different from those induced by physical stress.