Lesions of the cholinergic nuclei in the rat basal forebrain: excitotoxins vs. an immunotoxin

Infusion of the excitotoxins, ibotenic acid, quisqualic acid, or AMPA, into the medial septal nucleus, diagonal band, and the nucleus basalis magnocellularis of rats produced less cholinergic cell loss as assessed by choline acetyltransferase activity in the projection fields, cortex and hippocampus, than that obtainable by intraventricular administration of the immunotoxin, 192 IgG-saporin. All excitotoxins produced reductions in tissue levels of some monoamines, while no decreases were found for the immunotoxin. All toxins produced acquisitional impairment in the hidden platform water maze. This behavioral deficit was slightly greater for the excitotoxic-lesioned rats than for those given 192 IgG-saporin at a dose which produced ChAT depletions similar to the most potent excitotoxin (AMPA). This supports the idea that some of the behavioral effects produced by excitotoxic lesions are due to the cholinergic basal forebrain lesion and some are due to noncholinergic damage.