DYSFUNCTION OF CHOLINERGIC AND DOPAMINERGIC NEURONAL SYSTEMS IN BETA-AMYLOID PROTEIN-INFUSED RATS

Accumulations of beta-amyloid protein are characteristic and diagnosti c features of the brain of Alzheimer's disease patients; however, the physiological role of this protein in CNS is unknown. We have previous ly reported that continuous infusion of beta-amyloid protein into rat cerebral ventricle impairs learning ability and decreases choline acet yltransferase activity, a marker enzyme of cholinergic neuron. In this study, the effects of beta-amyloid protein infusion on the release of neurotransmitters in cholinergic and dopaminergic neuronal systems we re investigated by using an in vivo brain microdialysis method. Nicoti ne-stimulated release of acetylcholine and dopamine in these animals w as significantly lower than that in vehicle-infused rats. Further, dop amine release induced by high-K stimulation was decreased in beta-amyl oid protein-infused rats compared with vehicle-infused rats. These res ults suggest that the release of the two transmitters, acetylcholine a nd dopamine, was decreased by beta-amyloid protein and that learning d eficits observed in the beta-amyloid protein-infused rats are partly d ue to the impairment of neurotransmitter release. Furthermore, continu ous infusion of beta-amyloid protein may be a useful method to produce the animal model of Alzheimer's disease.