(192)IGG-SAPORIN IMMUNOTOXIN AND IBOTENIC ACID LESIONS OF NUCLEUS BASALIS AND MEDIAL SEPTUM PRODUCE COMPARABLE DEFICITS ON DELAYED NONMATCHING TO POSITION IN RATS

The recently developed immunotoxin, (192)IgG-Saporin (192-SAP), was co mpared with the standard excitotoxin, ibotenic acid, on two measures: (1) the extent of deficits on performance of a working memory task, de layed nonmatching-to-position (DNMTP), and (2) sensitivity to scopolam ine on this task. Rats were extensively pretrained in an operant, spat ial DNMTP memory task, then given combined site-specific lesions of th e medial septum/diagonal band and nucleus basalis magnocellularis usin g either ibotenic acid (IBO) or low doses of the selective cholinergic immunotoxin 192-SAP. When compared with sham controls, both IBO and 1 92-SAP lesioned rats showed significant delay-independent reductions i n DNMTP choice accuracy. Both 192-SAP and IBO lesioned rats showed inc reased sensitivity to a threshold dose of scopolamine, 0.15 mg/kg i.p. , on DNMTP, as compared with sham-lesioned controls. When the rats wer e assessed at 18 weeks postlesioning, levels of choline acetyltransfer ase were depleted in the hippocampus in both IBO and 192-SAP lesioned groups. These findings suggest that 192-SAP, a cholinergically selecti ve neurotoxin, is as effective as an excitotoxin when microinjected in to cholinergic cell bodies of the basal forebrain, producing deficits in behavioral tasks that persist for several weeks.