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.
Laboratory of Molecular and Integrative Neuroscience, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
B C
BC
Rogers
H A
HA
Tilson
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