Dopamine release in the prefrontal cortex during stress is reduced by the local activation of glutamate receptors.

Using microdialysis, we investigated the effects of the ionotropic glutamatergic agonists N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) on the stress-induced dopamine release in the prefrontal cortex of the freely moving rat. Handling-stress during 40 min increased extracellular dopamine by 195% and dopamine metabolites dihydroxyphenilacetic acid (DOPAC) by 120% and homovallinic acid (HVA) by 155% of baseline, but it did not modify extracellular glutamate, in the prefrontal cortex. Both NMDA (100 microM) and AMPA (20 microM), perfused through the microdialysis probe in the prefrontal cortex simultaneously to stress, significantly reduced the stress-induced dopamine release. These same doses or lower doses of NMDA (20 and 100 microM) and AMPA (1 and 20 microM) did not significantly modify basal dopamine release in the prefrontal cortex, but higher doses of these glutamatergic agonists significantly decreased (NMDA 500 microM) or increased (AMPA 100 microM) basal dopamine release in this area of the brain. These results show that the local activation of prefrontal glutamatergic ionotropic receptors reduces the stress-induced dopamine release in the prefrontal cortex of the rat.