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.
Lipartiti
M
M
Fidia Research Laboratories, Abano Terme (PD), Italy.
Fadda
E
E
Savoini
G
G
Siliprandi
R
R
Sautter
J
J
Arban
R
R
Manev
H
H
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001927:Brain Diseases / Q000139:chemically induced* / Q000503:physiopathology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000633:toxicity; D004357:Drug Synergism; D006624:Hippocampus / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D016202:N-Methylaspartate / Q000633:toxicity; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D009498:Neurotoxins / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000502:physiology*
D009498:Neurotoxins; D017470:Receptors, Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D016202:N-Methylaspartate