N-methylaspartate: an effective tool for lesioning basal forebrain cholinergic neurons of the rat

Gregory R. Stewart, Price Madelon, John W. Olney, Boyd K. Hartman, Constantino Cozzari

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The ability of the excitotoxin, N-methyl-d,l-aspartic acid (NMA), to destroy basal forebrain cholinergic (BFC) neurons was evaluated. NMA (100 nmol) was directly injected into the peripallidum, a region containing a proportionately large number of cortically-projecting BFC neurons. Cholineacetyltransferase (ChAT) activity 10 days later was markedly and significantly reduced (up to 62%) in the cortex ipsilateral to the lesion. NMA induced a focal lesion affecting BFC neurons without damaging axons of passage or causing lesions distant from the site of injection. ChAT immunohistochemistry (IHC) was used to directly demonstrate loss of ChAT-positive neurons from the lesion site. This loss persisted at all survival times examined, from 2 days to 7.5 months post-injection.

Original languageEnglish (US)
Pages (from-to)377-382
Number of pages6
JournalBrain Research
Issue number1-2
StatePublished - Mar 26 1986
Externally publishedYes

Bibliographical note

Funding Information:
Supported in part by NIH Grants MH37967. NS12311 and AG05681. Research Scientist Award MH38894 (J.W.O.) and a Lichtenstein grant. We thank Sandra Kalmbach and Sophia Goodman, respectively, for excellent assistance in immunohistochemical procedures and preparation of the manuscript.


  • N-methyl-d,l-aspartic acid
  • basal forebrain
  • cholineacetyltransferase
  • excitoxin
  • immunohistochemistry
  • lesion
  • rat


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