Cholinergic lesions of the rat brain by ibotenic acid and 192 IgG-saporin: effects on somatostatin, substance P and neuropeptide Y levels in the cerebral cortex and the hippocampus

Impairment of the basal forebrain cholinergic system is an important change in the brains of Alzheimer's disease patients. Various neurotoxins have been used to achieve this in animal models. In this study the effects of chemical lesions by ibotenic acid (IBO), a glutamate analogue and by 192 IgG-saporin, a highly specific immunotoxin against cholinergic neurons, were investigated. The toxins were delivered stereotaxically into the brains of young Sprague-Dawley rats which were later sacrificed by decapitation. Choline acetyltransferase (ChAT) activity was measured by radioenzymatic assay and substance P (SP), neuropeptide Y (NPY) and somatostatin (SOM) levels by radioimmunoassay. Decreased ChAT and SOM levels were observed in the cortex and the hippocampus in both experiments. Cortical SP levels were increased after IBO lesions but were unaffected after 192 IgG-saporin lesions. NPY levels remained unchanged in both experiments. The results indicate that there were specific changes in neuropeptide contents in the cortex and hippocampus in response to cholinergic damage in the rat brain. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved