Investigations of neurotoxicity and neuroprotection within the nucleus basalis of the rat.
The present study investigated the specific ways by which cytotoxicity due to glutamate receptor stimulation could be attenuated by the administration of agonists and antagonists of the ionotropic and metabotropic glutamate receptors within the nucleus basalis magnocellularis (NBM) of rats as measured by cortical choline acetyltransferase activity. The results of these studies suggest that (1) the cytotoxicity of ibotenate to NBM cholinergic cells is not dependent upon stimulation of metabotropic glutamate receptors, but results from activation of N-methyl-D-aspartate (NMDA) receptors, (2) the cytotoxicity of quisqualate to cholinergic cells within the NBM is not dependent upon stimulation of NMDA or metabotropic receptors, and (3) the cytotoxicity of NMDA was prevented by administration (i.p.) of the un-competitive NMDA antagonist memantine (30 mg/kg), resulting in plasma levels of 2.5 micrograms/ml, a concentration known to block efficiently NMDA receptors in vitro. Finally, performance of a food-motivated, delayed-alternation task on a T-maze was impaired by injections of NMDA into the NBM, but was prevented by co-administration of NMDA with memantine.
Wenk
G L
GL
Arizona Research Laboratories, University of Arizona, Tucson 85724.
Danysz
W
W
Mobley
S L
SL
D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D001479:Basal Ganglia / Q000166:cytology / Q000201:enzymology / Q000473:pathology*; D001522:Behavior, Animal / Q000187:drug effects; D002540:Cerebral Cortex / Q000201:enzymology / Q000473:pathology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D008297:Male; D008559:Memantine / Q000097:blood / Q000494:pharmacology; D008569:Memory Disorders / Q000139:chemically induced; D016202:N-Methylaspartate / Q000633:toxicity; D009422:Nervous System Diseases / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control; D016318:Quisqualic Acid / Q000633:toxicity; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013028:Space Perception / Q000502:physiology
D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine; D008559:Memantine