EXCITATORY AMINO-ACIDS RELEASE ENDOGENOUS ACETYLCHOLINE FROM RAT STRIATAL SLICES - REGULATION BY GAMMA-AMINOBUTYRIC-ACID

Endogenous acetylcholine release from rat striatal slices in response to several excitatory amino acids and its regulation by gamma-aminobutyric acid were investigated using a chemiluminescent reaction to detect this release continuously. The amount of acetylcholine released by glutamate (1 μM) was 60% of that released by KCl (50 mM). Quisqualic acid and kainic acid, both 1 μM, elicited only half as much acetylcholine release as did 1 μM of glutamic acid or N-methyl-d-aspartate. Only the effects of glutamate or N-methyl-d-aspartate were blocked by α-aminoadipic acid, but not by glutamic acid diethylester, both at 100 μM. Gamma-aminobutyric acid modulated acetylcholine release evoked by either high potassium or glutamate. However, the inhibitory effect of gamma-aminobutyric acid was greater (54%) when the slices were stimulated by glutamate than when depolarized by KCl (40%). These actions were completely reversed by picrotoxin or bicuculline, both at 100 μM. It is concluded on the one hand that glutamate elicits acetylcholine release by acting on the N-methyl-d-aspartate receptor. On the other hand, gamma-aminobutyric acid inhibited to a greater extent endogenous acetylcholine release evoked by glutamate than that evoked by potassium. These findings suggest that gamma-aminobutyric acid exerts an important regulation on cholinergic neurons stimulated by the glutamatergic corticostriatal pathway. © 1990.