Deficit in selective and divided attention associated with cholinergic basal forebrain immunotoxic lesion produced by 192-saporin; Motoric/sensory deficit associated with Purkinje cell immunotoxic lesion produced by OX7-saporin

The immunotoxin 192-saporin, infused intracerebroventricularly into rats, d estroys cholinergic neurons in the basal forebrain nuclei. Doses required f or complete cholinergic loss also kill some Purkinje cells. The immunotoxin OX7-saporin, when infused intraventricularly into rats, destroys Purkinje cells in a pattern similar to that produced by 192-saporin, without affecti ng cholinergic neurons. Thus, we used OX7-saporin to distinguish behavioral effects of 192-saporin due to cerebellar damage versus those due to cholin ergic cell loss. Three doses of 192-saporin (1.6, 2.6, and 3.3 mu g/rat) we re chosen along with a dose of OX7-saporin (2.0 mu g/rat) that produced Pur kinje loss equivalent to the two highest doses of 192-saporin. Groups of Fi scher-344 rats were trained in the multiple choice reaction time task and r etested with more complex tasks after lesioning. They were also tested in t he water maze, passive avoidance, acoustic startle, and open field. The OX7 -saporin group exhibited changes in many tests suggesting hypermotility and sensory deficits. The 192-saporin groups differed from the OX7-saporin gro up when they displayed deficits in multiple choice reaction time tasks in w hich novel challenges were introduced, including sessions with a noise dist racter, shortened and lengthened intertrial intervals, and use of nine inst ead of five sources of light stimulus. The 192-saporin groups showed no imp airment in the other tasks. The cholinergic basal forebrain lesion may mask some of the effects of cerebellar damage up to a threshold after which eff ects of Purkinje cell loss predominate when 192-saporin is administered int raventricularly. (C) 1999 Academic Press.