METABOTROPIC GLUTAMATE ANTAGONIST, MCPG, TREATMENT OF TRAUMATIC BRAININJURY IN RATS

The metabotropic glutamate receptor (mGluR) antagonist, alpha-methyl-4 -carboxyphenylglycine (MCPG) was administered into the left lateral ve ntricle 5 min prior to fluid percussion traumatic brain injury (TBI) i n the rat. A single 5.0 mu l ventricular infusion of the active isomer , (+)-MCPG (0.2 mu mol), significantly reduced beam walking motor defi cits 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 mo l) nor the relatively inactive isomer, (-)-MCPG(0.2 mu mol) affected b ehavioral outcome. (+)-MCPG (0.2 mu mol) did not affect systemic hemod ynamic responses to injury. These results suggest that TBI induced act ivation of mGluRs contributes to behavioral morbidity and that blockad e of certain mGluR subtypes (mGluR(1), mGluR(5) and/or mGluR(2)) may r educe these pathophysiological responses.