Metabotropic glutamate antagonist, MCPG, treatment of traumatic brain injury in rats

The metabotropic glutamate receptor (mGluR) antagonist, α-methyl-4-car{ballot box}yphenylglycine (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 μl ventricular infusion of the active isomer, (+)-MCPG (0.2 μmol), 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 μmol) nor the relatively inactive isomer, (-)-MCPG (0.2 μmol) affected behavioral outcome. (+)-MCPG (0.2 μmol) 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 (mGluR₁, mGluR₅ and/or mGluR₂) may reduce these pathophysiological responses.