Glutamate regulation of dopamine release in guinea pig striatal slices

The effect of L-glutamic acid (L-Glu) on basal and electrically evoked [3H]-dopamine efflux in guinea pig striatal slices was studied. In the presence of magnesium, L-Glu significantly increased spontaneous [3H]-dopamine efflux. This response was unaffected by the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), the non-competitive NMDA receptor antagonist, D-5-methyl-10,11, dihydro-5-H-dibenzo-[a,d]-cyclohepten-5,10-imine maleate (MK-801), the glycine antagonist 7-chlorokynurenic acid (7-CL-KYN) and by the metabotropic receptor antagonist (+)-alpha-methyl-4-carboxyphenyl-glycine (alpha-M4CPG) and L-2-amino-3-phosphonopropionic acid (L-AP3). However, the metabotropic glutamate receptor agonist, trans-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD), increased spontaneous [3H]-dopamine efflux, as did L-Glu, and this response was completely counteracted by alpha-M4CPG. In the absence of magnesium, L-Glu induced a concentration-dependent increase in basal [3H]-dopamine efflux, which was prevented by MK-801. In electrically stimulated striatal slices L-Glu, applied 25 min before the stimulation, concentration-dependently increased the [3H]-dopamine efflux both in the presence and in the absence of magnesium. This effect was completely prevented by CNQX, but not by MK-801 or DL-2-amino-5-phosphono-pentanoic acid (AP5). On the contrary, L-Glu, applied during electrical stimulation (2 min) in the absence of Mg2+, increased the [3H]-dopamine efflux to 200%, and this effect was partly counteracted by MK-801. These results provide evidence that different subtypes of excitatory amino acid receptors modulate [3H]-dopamine efflux depending on the functional state (rest or activity) of the nerve endings. The spontaneous [3H]-dopamine efflux appears to be controlled by metabotropic receptors in the presence of Mg2+ and by NMDA receptors in its absence. Conversely, the AMPA/kainate receptors facilitate the electrically evoked [3H]-dopamine efflux in the presence of Mg2+, whereas the NMDA receptors appeared to be operative, in the absence of Mg2+, as long as L-Glu was applied simultaneously with the electrical stimulation.