L-trans-Pyrrolidine-2,4-dicarboxylic acid (L-trans-2,4-PDC) is an inhibitor of L-glutamate transport (K = 4.6 μM in rat brain synaptosomes). It inhibits radioligand binding to NMDA receptors by 13% but has no effect on AMPA or kainate receptors when used at a concentration of 100 μM. L-trans-2,4-PDC is neurotoxic to astrocyte-rich and astrocyte-poor rat cortical cultures (ECs = 320 and 50 μM, respectively), an effect that can be reversed by the NMDA antagonist MK-801 and glutamate-pyruvate transaminase but not the non-NMDA glutamate receptor antagonist CNQX . It induces efflux of the non-metabolizable glutamate analog [H]-D-aspartate in an extracellular sodium-dependent manner. In vivo, L-trans-2,4-PDC (0.05-0.2 μg/side) prevents amphetamine-induced hyperlocomotion in a dose-dependent manner in rats when injected directly into the nucleus accumbens. It also increases bladder intercontraction interval (ICI) without affecting postvoid residual or basal pressure in rats.