AGING-RELATED ALTERATIONS IN BEHAVIORAL ACTIVATION AND CEREBROVASCULAR INTEGRITY IN RATS ARE DOSE-DEPENDENTLY INFLUENCED BY NIMODIPINE

We investigated behavioral activation in response to a novel environment in young (3 months) and aged (30 months) Wistar rats, and found that in aged animals ambulation as well as head movements with sniffing (general vigilance) was significantly reduced. Aged animals to which 500, 860 or 1200 ppm nimodipine was administered in the daily food from the age of 24 up to 30 months showed increased ambulation and head movements, which was significant for the two higher doses. We also studied the effect of these three nimodipine doses on the occurrence of ultrastructural anomalies of cerebral cortical microvessels. Aging-related microvascular aberrations can be divided into 1) membranous inclusions within the basement membrane and 2) microvascular deposits, which include fibrosis and thickening of the basement membrane. The formation of membranous inclusions is not influenced by nimodipine treatment, but the incidence microvascular deposits was significantly reduced in all nimodipine treated groups vs. aged controls. The effect of the different nimodipine doses on microvascular deposits shows an inverted U-shape curve, with the most effective dose being 860 ppm. These data indicate that alterations in both behavioral activity and microvascular condition during aging are dose dependently improved by chronic nimodipine treatment.