INDUCTION OF HEAT-SHOCK-PROTEIN (HSP72) IN THE CINGULATE AND RETROSPLENIAL CORTEX BY DRUGS THAT ANTAGONIZE THE EFFECTS OF EXCITATORY AMINO-ACIDS

To address the issue of the cytotoxicity of glutamate antagonists, we administered representative agents to rats and used HSP72 immunocytoch emistry as a measure of neuronal injury in the brain. The doses studie d spanned the reported neuroprotective range for each compound, Some, but not all, glutamate antagonists induce neuronal injury in the brain . The non-competitive NMDA antagonists (MK801 and dextrorphan) demonst rate maximum toxicity. Competitive NMDA antagonists (CGS 19755 and MDL 100,453) may or may not induce neuronal injury depending on the parti cular compound. The polyamine site (SL 82.0715-10) antagonist does not result in neuronal injury. Cingulate and retrosplenial cortex neuroto xicity is not a ubiquitous feature of neuroprotective agents that bloc k excitotoxcity, but is limited to NMDA antagonists and may depend upo n the duration and completeness of the blockade of the NMDA receptor.