Spatial learning impairment in aged rats: comparing between aged basal forebrain lesioned and normal aged rats.

Normal aged rats (26 months) displayed significant impairments in learning the Morris water maze task as compared with young adult rats (3 months). The learning deficits of aged basal forebrain (BF)-lesioned rats (26 months; ethylcholine aziridinium ion was injected into the bilateral basal forebrain at 3 months age) were more severe than those of normal aged rats. Choline acetyltransferase (ChAT) in the frontal cortex of aged BF-lesioned rats activity was significantly reduced, but not in normal aged rats which level was almost the same as that in young adult rats. Histological examination showed that cholinergic fibers (acetylcholinesterase staining) in the frontal cortex reduced in aged BF-lesioned rats, but not in normal aged rats. The number of binding sites (Bmax) for [3H]vesamicol, a ligand for the vesicular acetylcholine transporter, in the frontal cortex of normal aged rats was significantly less than that in young adult rats, while the Bmax of aged BF-lesioned rats was higher than that of normal aged rats. The levels of monoamines and their metabolites in the frontal cortex and striatum but not hippocampus of aged BF-lesioned rats were markedly reduced as compared with those of normal aged and young adult rats. These results taken together indicate that normal aged and aged BF-lesioned rats exhibit learning deficits and that the differences of the severity of spatial learning deficits between normal aged and aged BF-lesioned rats may be due to, at least in part, the different properties of cathecolaminergic, serotonergic and cholinergic dysfunctions in the discrete brain sites.