Regulation of [3H]norepinephrine release by N-methyl-D-aspartate receptors in minislices from the dentate gyrus and the CA1-CA3 area of the rat hippocampus.

It has been reported previously that N-methyl-D-aspartic acid induces a significant release of [3H]norepinephrine preaccumulated in slices from the hippocampus. In the present study, we investigated whether there are regional differences in the hippocampus regarding this N-methyl-D-aspartate effect. In the absence of Mg2+, N-methyl-D-aspartate (10-200 microM) induced the release of [3H]norepinephrine from superfused minislices containing the dentate gyrus area or the CA1-CA3 region of the hippocampus. Such N-methyl-D-aspartate effects on [3H]norepinephrine release were significantly higher in the dentate gyrus than in the CA1-CA3 area. The N-methyl-D-aspartate effects in both hippocampal areas were also reduced significantly by D-2-amino-5-phosphonovaleric acid (50 microM), an antagonist of the N-methyl-D-aspartate receptor, and by tetrodotoxin, a blocker of the voltage-dependent Na+ channels. The extent of this reduction was the same in the dentate gyrus and the CA1-CA3 area. Further experiments, conducted in the presence of Mg2+, demonstrated that N-methyl-D-aspartic acid increased K(+)-induced release of [3H]norepinephrine from dentate gyrus minislices but not from the CA1-CA3 area. The results are consistent with the existence of a higher density and/or different subtypes of N-methyl-D-aspartate receptors modulating [3H]norepinephrine release in the dentate gyrus as compared with the CA1-CA3 hippocampal area.