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 glutamat ergic agonists N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-meth ylisoxazole-4-propionic acid (AMPA) on the stress-induced dopamine release in the prefrontal cortex of the freely moving rat. Handling-stress during 4 0 min increased extracellular dopamine by 195% and dopamine metabolites dih ydroxyphenilacetic acid (DO PAC) by 120% and homovallinic acid (HVA) by 155 % of baseline, but it did not modify extracellular glutamate, in the prefro ntal cortex. Both NMDA (100 muM) and AMPA (20 muM), perfused through the mi crodialysis probe in the prefrontal cortex simultaneously to stress, signif icantly reduced the stress-induced dopamine release. These same doses or lo wer doses of NMDA (20 and 100 muM) and AMPA (1 and 20 muM) did not signific antly modify basal dopamine release in the prefrontal cortex, but higher do ses of these glutamatergic agonists significantly decreased (NMDA 500 muM) or increased (AMPA 100 muM) basal dopamine release in this area of the brai n. These results show that the local activation of prefrontal glutamatergic ionotropic receptors reduces the stress-induced dopamine release in the pr efrontal cortex of the rat. (C) 2001 Elsevier Science Inc.