Distinct actions of endogenous excitatory amino acids on the outflow of dopamine in the nucleus accumbens

Intracerebral microdialysis was utilized to assess the effect of endogenous excitatory amino acids (EAA), l-glutamate (GLU) and l-aspartate (ASP), on the extracellular levels of dopamine in the rat nucleus accumbens. Both ASP and GLU produced a release response at a concentration range of 1 to 10 mM. GLU was generally less efficacious in increasing dopamine outflow; at 5 and 10 mM, the maximum effect exerted by GLU was significantly less than that observed with ASP. The specific N-methyl-D- aspartate (NMDA) antagonist 2-amino-5-phosphonopentanoic (AP5) acid was more effective in attenuating the actions of 5 and 10 mM ASP than the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3- dione (CNQX). On the other hand, the stimulatory actions of 5 and 10 mM GLU were more effectively decreased with CNQX when compared with AP5. Perfusion of tetrodotoxin before application of either GLU or ASP blocked the excitatory effect of these amino acids on dopamine overflow. These results suggest that in the nucleus accumbens, ASP and GLU may increase dopamine release through distinct mechanisms and that their stimulatory action is dependent on axonal impulse flow.