Dysfunction of cholinergic and dopaminergic neuronal systems in beta-amyloid protein--infused rats.
Accumulations of beta-amyloid protein are characteristic and diagnostic features of the brain of Alzheimer's disease patients; however, the physiological role of this protein in CNS is unknown. We have previously reported that continuous infusion of beta-amyloid protein into rat cerebral ventricle impairs learning ability and decreases choline acetyltransferase 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 were investigated by using an in vivo brain microdialysis method. Nicotine-stimulated release of acetylcholine and dopamine in these animals was significantly lower than that in vehicle-infused rats. Further, dopamine release induced by high-K stimulation was decreased in beta-amyloid protein-infused rats compared with vehicle-infused rats. These results suggest that the release of the two transmitters, acetylcholine and dopamine, was decreased by beta-amyloid protein and that learning deficits observed in the beta-amyloid protein-infused rats are partly due to the impairment of neurotransmitter release. Furthermore, continuous infusion of beta-amyloid protein may be a useful method to produce the animal model of Alzheimer's disease.
Itoh
A
A
Department of Neuropsychopharmacology, Nagoya University School of Medicine, Japan.
Nitta
A
A
Nadai
M
M
Nishimura
K
K
Hirose
M
M
Hasegawa
T
T
Nabeshima
T
T
D000109:Acetylcholine / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D005625:Frontal Lobe / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D017551:Microdialysis; D009538:Nicotine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats
D016229:Amyloid beta-Peptides; D009538:Nicotine; D000109:Acetylcholine; D011188:Potassium; D004298:Dopamine