Preservation of hippocampal NMDA receptors may be crucial for spatial learning after epileptic seizures in rats.
Sustained electrical stimulation of the perforant pathway (PP) was used to induce hippocampal seizures in conscious rats. About 4.5 h prior to stimulation, animals were given i.p. injections of either saline or CGP 39551 (10 mg/kg), a competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor. When tested 2 weeks later in water maze, the saline pretreated rats showed a severe impairment in spatial learning whereas the animals treated with CGP 39551 had the same escape latencies as the non-stimulated controls. Histological evaluation of cellular degeneration revealed that the number of somatostatin-immunoreactive (SOM-IR) neurons in both stimulated groups was reduced almost equally, but in the CGP 39551 treated animals pyramidal cell damage was partly protected. However, in contrast to the placebo group, NMDA-sensitive [3H]glutamate binding in strata radiatum and oriens of the CA1 area was not significantly reduced in the CGP 39551 group. Thus, the present results suggest that the CGP 39551 treatment was able to protect against the delayed phase of the excitotoxic cell damage, and that the preservation of NMDA receptors partly accounts for the good learning ability of the CGP 39551 pretreated, PP-stimulated rats.
Lahtinen
H
H
Department of Neurology, A.I. Virtanen Institute, University of Kuopio, Finland.
Ylinen
A
A
Hyvönen
M
M
Sirviö
J
J
Miettinen
R
R
Riekkinen
P J
PJ
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003072:Cognition Disorders / Q000209:etiology / Q000523:psychology; D004558:Electric Stimulation; D004827:Epilepsy / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D007858:Learning / Q000502:physiology*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism; D013028:Space Perception / Q000502:physiology*
D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; C064540:CGP 39551; D018698:Glutamic Acid; D013004:Somatostatin; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate