Abstract
The recently developed immunotoxin, 192IgG-Saporin (192-SAP), was compared with the standard excitotoxin, ibotenic acid, on two measures: (1) the extent of deficits on performance of a working memory task, delayed nonmatching-to-position (DNMTP), and (2) sensitivity to scopolamine on this task. Rats were extensively pretrained in an operant, spatial DNMTP memory task, then given combined site-specific lesions of the medial septum/diagonal band and nucleus basalis magnocellularis using either ibotenic acid (IBO) or low doses of the selective cholinergic immunotoxin 192-SAP. When compared with sham controls, both IBO and 192-SAP lesioned rats showed significant delay-independent reductions in DNMTP choice accuracy. Both 192-SAP and IBO lesioned rats showed increased sensitivity to a threshold dose of scopolamine, 0.15 mg/kg i.p., on DNMTP, as compared with sham-lesioned controls. When the rats were assessed at 18 weeks postlesioning, levels of choline acetyltransferase were depleted in the hippocampus in both IBO and 192-SAP lesioned groups. These findings suggest that 192-SAP, a cholinergically selective neurotoxin, is as effective as an excitotoxin when microinjected into cholinergic cell bodies of the basal forebrain, producing deficits in behavioral tasks that persist for several weeks.
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