Blockade of metabotropic glutamate receptors protects rat CA1 neurons from hypoxic injury.

The possible involvement of the metabotropic glutamate receptor in mechanisms of posthypoxic neuronal damage was investigated in an in-vitro model of mild hypoxia with the stereoselective antagonist L-2-amino-3-phosphonopropionate (L-AP3). When 300 microM L-AP3 was present during hypoxia the evoked field potentials (population EPSP and population spike in the CA1 region of the hippocampus) recovered to about 80-100% of baseline values. The recovery without drug treatment reached only 40-75%. The NMDA antagonist D,L-2-amino-5-phosphonovalerate (100 microM) was equally effective as L-AP3, whereas the less effective and less specific isomer D-AP3 (300 microM) did not show any protective effect. The results suggest that the activation of metabotropic glutamate receptors plays a role in hypoxic injury.