192 IGG-SAPORIN .1. SPECIFIC LETHALITY FOR CHOLINERGIC NEURONS IN THEBASAL FOREBRAIN OF THE RAT

An immunotoxin (IT) composed of a monoclonal antibody to the nerve gro wth factor (NGF) receptor, 192 IgG, chemically linked to saporin, 192 IgG-saporin, was shown to selectively reduce forebrain choline acetylt ransferase (ChAT) activity in the rat brain following intraventricular administration. In order to determine if the IT was killing NGF recep tor-positive neurons in the CBF (rather than simply suppressing the ch olinergic phenotype in these cells), a population of neurons in the nu cleus basalis magnocellularis (NBM) was prelabeled by an intracortical injection of the neurotracer Fluoro-Gold (FG) 1 week before intravent ricular injections of IT or control substances (reduced IT or phosphat e-buffered saline). We found that there were very few double-labeled ( i.e. FG-labeled and ChAT-positive) neurons remaining in the NBM of IT- treated animals. The absolute number of FG-labeled neurons in the NBM of IT-treated animals was reduced by a number similar to the counts of double-labeled neurons in the NBM of control animals. Our conclusion is that the IT is preferentially lethal to cholinergic neurons in the NBM. Due to its ability to selectively kill cholinergic neurons in the CBF and concomitantly spare noncholinergic neurons with similar morph ology and projections, 192 IgG-saporin can be used to produce a select ive model of CBF deficit in the rat.