GLUTAMATE REGULATION OF DOPAMINE RELEASE IN GUINEA-PIG STRIATAL SLICES

The effect of L-glutamic acid (L-Glu) on basal and electrically evoked [H-3]-dopamine efflux in guinea pig striatal slices was studied. In t he presence of magnesium, L-Glu significantly increased spontaneous [H -3]-dopamine efflux. This response was unaffected by the non-NMDA rece ptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), the non- competitive NMDA receptor antagonist, 1,dihydro-5-H-dibenzo-[a,d]-cycl ohepten-5,10-imine maleate (MK-801), the glycine antagonist 7-chloroky nurenic acid (7-CL-KYN) and by the metabotropic receptor antagonist ()-alpha-methyl-4-carboxyphenyl-glycine (alpha-M4CPG) and L-2-amino-3-p hosphonopropionic acid (L-AP3). However, the metabotropic glutamate re ceptor agonist, trans-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACP D), increased spontaneous [H-3]-dopamine efflux, as did L-Gly and this response was completely counteracted by alpha-M4CPG. In the absence o f magnesium, L-Glu induced a concentration-dependent increase in basal [H-3]-dopamine efflux, which was prevented by MK-801. In electrically stimulated striatal slices L-Glu, applied 25 min before the stimulati on, concentration-dependently increased the [H-3]-dopamine efflux both in the presence and in the absence of magnesium. This effect was comp letely prevented by CNQX, but not by MK-801 or DL-2-amino-5-phosphono- pentanoic acid (AP5). On the contrary, L-Glu, applied during electrica l stimulation (2 min) in the absence of Mg2+, increased the [H-3]-dopa mine 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 [H-3]-dopamine efflux depending on the functional state (rest or activity) of the nerve endings. The spontane ous [H-3]-dopamine efflux appears to be controlled by metabotropic rec eptors in the presence of Mg2+ and by NMDA receptors in its absence. C onversely, the AMPA/kainate receptors facilitate the electrically evok ed [H-3]-dopamine efflux in the presence of Mg2+, whereas the NMDA rec eptors appeared to be operative, in the absence of Mg2+, as long as L- Glu was applied simultaneously with the electrical stimulation. Copyri ght (C) 1996 Elsevier Science Ltd