Age-related reductions in brain cholinergic and dopaminergic indices in two rat strains differing in longevity

Abstract

We have recently reported that inbred Wistar-Kyoto rats which are highly reactive to stressful stimuli, have a much shorter mean life-span (21.5) compared to the less reactive Brown-Norway rats (31.0 +/- 4.5 months). In the present study we found a reduction in forebrain cholinergic neurotransmission indices in 24-month-old Wistar-Kyotos but not in Brown-Norways as compared to their respective young (3-month-old) counterparts. Also only in Wistar-Kyotos dopamine uptake was reduced in the aged striatum, but in the septum it remained unchanged in both strains. In Brown-Norways, age-related changes were observed only in choline acetyltransferase activity and only in brain regions known to contain mainly cholinergic nerve cell bodies. We conclude that at 24 months of age, reductions in brain cholinergic and dopaminergic neurotransmission are more prominent in the highly stress-reactive and shorter-lived Wistar-Kyoto strain, and may be genetically determined.