The mesoaccumbens dopamine in coping with stress.

Mesoaccumbens dopamine (DA) is involved in the stress response. Although neural mechanisms involved in stress are of paramount importance for both clinical and preclinical research, the results of studies on the stress response by mesoaccumbens DA have received little attention. Therefore, we aimed to review these results and propose a role for mesoaccumbens DA in coping with stress. The data reviewed support the view that fluctuations of tonic levels characterize the mesoaccumbens DA stress response. Stress-induced increase of tonic DA levels in nucleus accumbens (NAc) supports expression of responses aimed at removing and avoiding the stressor through activation of DA D2 receptors, whereas inhibition of DA is associated with cessation of active defensive responses. In novel unescapable/uncontrollable stressful conditions tonic levels of DA in NAc show an initial increase followed by a decrease below pre-stress levels that lasts as long as the stressful situation. This biphasic response fits with the dynamics of the primary and secondary appraisal of a stressor that cannot be removed, escaped or controlled by the organism. In fact, NAc DA fluctuations are controlled by the medial pre-frontal cortex, which is involved in stress appraisal. We propose that enhanced mesoaccumbens DA supports expression of active coping strategies against an event appraised as a stressor and that inhibition of DA is required for passive coping with stressful situations appraised as unescapable/uncontrollable.