Group I metabotropic glutamate receptor agonist causes neurodegeneration in rat hippocampus.

Activation of group I metabotropic glutamate receptors results in an increase in cytosolic Ca2+. High levels of free Ca2+ in the cytoplasm could be toxic to cells. We now report that intracerebroventricular injections of a group I metabotropic glutamate receptor agonist (S)-3,5-dihydroxyphenylglycine (DHPG) leads, within hours, to changes in the distribution of ionotropic glutamate receptors in the hippocampus and a delayed (4-7 days) loss of hippocampal pyramidal neurons. Injection of glutamate transporter substrates resulted in no loss of neurons and the administration of an NMDA agonist produced lesions different from those caused by (S)-DHPG. These results suggest that the activation of metabotropic glutamate receptors of group I in vivo may indeed result in neurotoxic events.