Effects of amyloid-beta-(25-35) on passive avoidance, radial-arm maze learning and choline acetyltransferase activity in the rat.

To investigate the neurotoxicity of amyloid-beta-(25-35), which is thought to be the active site of amyloid-beta, the peptide was injected into the lateral ventricle of rats. A single intracerebroventricular (i.c.v.) injection of amyloid-beta-(25-35) at a dose of 15 nmol/rat induced a marked decrease in latency in step-through passive avoidance task. Amyloid-beta-(35-25), reverse sequence of amyloid-beta-(25-35), was without harmful effects on passive avoidance performance. The amyloid-beta-(25-35) at a dose of 5 or 15 nmol/rat impaired radial-arm maze performance, and induced a decrease in choline acetyltransferase activity in the medial septum, cortex and hippocampus, but not in the basal forebrain. The number of choline acetyltransferase-immunoreactive cells in the medial septum was decreased, in conformity with the decrease in choline acetyltransferase activity of the area. These results suggest that learning and cognitive disturbance induced by i.c.v. injection of amyloid-beta-(25-35) is associated with the dysfunction of cholinergic neuronal system in the brain.