Learning deficiency and alterations in acetylcholine receptors and proteinkinase C in the brain of senescence-accelerated mouse (SAM)-P10

The senescence-accelerated mouse (SAM) is known to be a murine model for ac celerated aging. A novel inbred SAMP10 has shown age-related brain atrophy and learning deficiency. In the present study, we investigated the changes in learning ability and in ligand binding with muscarinic acetylcholine (mA Ch) receptors, ct adrenoceptors and protein kinase C in SAMP10. In Morris's water maze task, in a control strain of SAMR1 at 9 months, the escape late ncy and path length decreased with increasing trial days, in contrast, esca pe latency and path length did not decrease in SAMP10. These results indica te that SAMP10 exhibits learning deficiency. The ligand binding activity of mACh receptors decreased in the hippocampus of SAMP10 and the protein kina se C level in the hippocampus of SAMP10 was lower than that of SAMR1. On th e other hand, there was no significant difference between SAMR1 and SAMP10 regarding ligand binding activity of alpha(1) and alpha(2) adrenoceptors. T hus, a reduction of mACh receptors and protein kinase C. in the brain seems to underlie dysfunction of learning and memory in SAMP10. (C) 7000 Elsevie r Science Ireland Ltd. All rights reserved.