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 ?M) was 60% of that released by KCl (50 mM). Quisqualic acid and kainic acid, both 1 ?M, elicited only half as much acetylcholine release as did 1 ?M of glutamic acid or N- methyl- d -aspartate . Only the effects of glutamate or N- methyl- d -aspartate were blocked by ?-aminoadipic acid, but not by glutamic acid diethylester, both at 100 ?M. 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 ?M. 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.