Future planning and behavioral modification is thought to require experience-dependent plasticity in neuronal circuits involving the prefrontal cortex, nucleus accumbens and amygdala. Dopamine has been implicated in such plasticity; however, the nature of the adaptive response of dopamine systems to emotionally salient experiences is poorly understood. We determined whether the dopaminergic response to a given stimulus changes after the first exposure to that stimulus and whether this alteration is stimulus specific. Dopamine release was measured in the prefrontal cortex and the nucleus accumbens in response to two aversive but qualitatively distinct stimuli, physical restraint and electrical microstimulation of basolateral amygdala. In the prefrontal cortex, the first exposure to restraint or amygdala stimulation produced similar increases in dopamine release. The second exposure to restraint resulted in an attenuated response (- 36%) whereas the second exposure to amygdala stimulation produced a potentiated response (+ 110%). Cross-modal potentiation of response occurred with both stimuli. These adaptive changes were specific to the prefrontal cortex and were not observed in the nucleus accumbens. These findings demonstrate that prefrontal cortical dopamine output adapts after a single exposure to stimuli with emotional salience. The direction of this adaptation, however, is not uniform and depends on the nature of the stimulus.