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

Neurobiol Learn Mem. 1999 May;71(3):325-52. doi: 10.1006/nlme.1998.3884.


The immunotoxin 192-saporin, infused intracerebroventricularly into rats, destroys cholinergic neurons in the basal forebrain nuclei. Doses required for 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 affecting cholinergic neurons. Thus, we used OX7-saporin to distinguish behavioral effects of 192-saporin due to cerebellar damage versus those due to cholinergic cell loss. Three doses of 192-saporin (1.6, 2.6, and 3.3 micrograms/rat) were chosen along with a dose of OX7-saporin (2.0 micrograms/rat) that produced Purkinje loss equivalent to the two highest doses of 192-saporin. Groups of Fischer-344 rats were trained in the multiple choice reaction time task and retested with more complex tasks after lesioning. They were also tested in the 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 group when they displayed deficits in multiple choice reaction time tasks in which novel challenges were introduced, including sessions with a noise distractor, shortened and lengthened intertrial intervals, and use of nine instead of five sources of light stimulus. The 192-saporin groups showed no impairment in the other tasks. The cholinergic basal forebrain lesion may mask some of the effects of cerebellar damage up to a threshold after which effects of Purkinje cell loss predominate when 192-saporin is administered intraventricularly.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / adverse effects*
  • Attention / drug effects*
  • Avoidance Learning / drug effects
  • Cerebellum / drug effects
  • Cholinergic Fibers / drug effects*
  • Cognition Disorders / chemically induced*
  • Dose-Response Relationship, Drug
  • Hyperkinesis / chemically induced*
  • Immunoconjugates
  • Immunotoxins / adverse effects*
  • Injections, Intraventricular
  • Maze Learning / drug effects
  • N-Glycosyl Hydrolases
  • Prosencephalon / drug effects*
  • Purkinje Cells / drug effects*
  • Rats
  • Reaction Time / drug effects
  • Reflex, Startle / drug effects
  • Ribosome Inactivating Proteins, Type 1
  • Saporins
  • Sensation Disorders / chemically induced*
  • Spatial Behavior / drug effects


  • 192 IgG-saporin
  • Antibodies, Monoclonal
  • Immunoconjugates
  • Immunotoxins
  • OX7-saporin
  • Ribosome Inactivating Proteins, Type 1
  • N-Glycosyl Hydrolases
  • Saporins