Brain glutamate inhibition and amnesia: evidence provided by proline analog action.

The action of proline and its analog as glutamate antagonists was investigated in CNS tissue of the neonatal chick. Avian brain slices were incubated in low concentrations of L-proline, D-proline, DL-3,4-dehydro-proline, L-prolyl-L-proline, or in avian physiological salt solution before depolarization was induced by application of 45 mM K+. Glutamate was determined in the efflux material collected both before and after tissue stimulation. The release of endogenous glutamate was inhibited significantly by exposure to L-proline, DL-3,4-dehydroproline and L-prolyl-L-proline. The degree of glutamate inhibition correlated with the amnestic potency of these substances. The manner in which these results strengthen the hypothesis of glutamate involvement in memory processes is discussed.