In rats, the metabotropic glutamate receptor-triggered hippocampal neuronal damage is strain-dependent.

The effect of intrahippocampal (i.h.) and intraocular (i.o.) administration of the selective metabotropic glutamate receptor (mGluR) agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) was studied in different rat strains. A massive hippocampal damage was observed in CD/SD and Fischer 344 but not in SD/Rij and Brown Norway rats 7 days following the i.h. injection of 1S,3R-ACPD, while no retinal damage was observed following its i.o. administration. Moreover, 1S,3R-ACPD reduced the N-methyl-D-aspartate (NMDA) toxicity in the retina of both CD/SD and SD/Rij rats. Regardless of its toxic action on hippocampal neurons the i.h. injection of 1S,3R-ACPD caused an acute stimulation of motor activity in both CD/SD and SD/Rij rats. This effect was blocked by the intracerebroventricular (i.c.v.) administration of the putative mGluR antagonist L-2-amino-3-phosphono-propionic acid (L-AP3). It is suggested that the differential expression of mGluR subtypes might determine their role in brain pathology.