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 microliters ventricular infusion of the active isomer. (+)-MCPG (0.2 mumol), 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 (0.2 mumol) affected behavioral outcome. (+)-MCPG (0.2 mumol) 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.
Gong
Q Z
QZ
Department of Psychology, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298-0683, USA.
Delahunty
T M
TM
Hamm
R J
RJ
Lyeth
B G
BG
D000704:Analysis of Variance; D000818:Animals; D001565:Benzoates / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001930:Brain Injuries / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D002552:Cerebral Ventricles; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects; D007263:Infusions, Parenteral; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*
D001565:Benzoates; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; C079694:alpha-methyl-4-carboxyphenylglycine; D005998:Glycine