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192 IgG-saporin, an immunotoxin targeted at the low affinity NGF receptor, was infused into the lateral ventricle of rat brain. Three days and one week post lesion, choline acetyltransferase activity was markedly decreased in cortex, hippocampus, olfactory bulbs, and septum (brain regions innervated by the cholinergic neurons of the basal forebrain) with no change in cerebellum, striatum or pons. Measurement of monoamine levels revealed increases in HVA, DOPAC and dopamine, primarily in the olfactory bulbs at the 28-day time point only, suggesting a compensation for cholinergic inactivity. High levels of basal forebrain cholinergic lesioning can be obtained with this immunotoxin with minimal or no effects on monoaminergic or other cholinergic systems.
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