192IgG-Saporin immunotoxin and ibotenic acid lesions of nucleus basalis and medial septum produce comparable deficits on delayed nonmatching to position in rats

John K. Robinson, Gary L. Wenk, Ronald G. Wiley, Douglas A. Lappi, Jacqueline Crawley

Research output: Contribution to journalArticle

21 Scopus citations

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 DNMP 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 DNMPT, 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 an effective as an excitotoxin when microinjected into cholinergic cell bodies of the basal forebrain, producing deficits in behavioral tasks that persist for several weeks.

Original languageEnglish (US)
Pages (from-to)179-186
Number of pages8
JournalPsychobiology
Volume24
Issue number3
StatePublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

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