METABOTROPIC GLUTAMATE ANTAGONIST, MCPG, TREATMENT OF TRAUMATIC BRAIN INJURY IN RATS

The metabotropic glutamate receptor (mGluR) antagonist, alpha-methyl-4-carboxyphenylglycine (MCPG) was administered into the left lateral ventricle 5 min prior to fluid percussion traumatic brain injury (TBI) in the rat. A single 5.0 mu l ventricular infusion of the active isomer, (+)-MCPG (0.2 mu mol), significantly reduced beam walking motor deficits on days 1-5 after injury and learning/memory deficits measured on days 11-15 after injury. Neither a lower dose of (+)-MCPG (0.02 mu mol) nor the relatively inactive isomer, (-)-MCPG(0.2 mu mol) affected behavioral outcome. (+)-MCPG (0.2 mu mol) did not affect systemic hemodynamic responses to injury. These results suggest that TBI induced activation of mGluRs contributes to behavioral morbidity and that blockade of certain mGluR subtypes (mGluR(1), mGluR(5) and/or mGluR(2)) may reduce these pathophysiological responses.