Stereospecificity of N-MDA-induced functional deficits.
Male Fischer-344N rats were pretreated bilaterally with intrahippocampal (D) (-)-2-amino-7-phosphonoheptanoic acid [(D)-2-APH] (2.5, 5.0 and 10 micrograms/site), a competitive N-methyl-d-aspartate (NMDA) antagonist, prior to the administration of bilateral N-MDA (10 micrograms/site). (D)-2-APH completely attenuated NMDA-induced hyperactivity and water maze acquisition deficits. (D)-2-APH also attenuated hippocampal pyramidal and granule cell loss induced by NMDA. These effects were stereospecific since pretreatment of the isomer L-(+)-2-APH (10 micrograms/site) had no effect on hyperactivity and water maze acquisition deficits produced by NMDA. In addition, (L)-2-APH provided no protection from NMDA-induced hippocampal granule and pyramidal cell loss. Together, these results suggest that the intrahippocampal administration of NMDA might serve as a useful in vivo model for evaluating the effects associated with the overactivation of NMDA receptors.
Rogers
B C
BC
Laboratory of Molecular and Integrative Neuroscience, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Tilson
H A
HA
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D007858:Learning / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D016202:N-Methylaspartate; D051381:Rats; D011916:Rats, Inbred F344; D013237:Stereoisomerism
D000596:Amino Acids; D001224:Aspartic Acid; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; C031231:2-amino-7-phosphonoheptanoic acid