CHRONIC NIMODIPINE TREATMENT IN AGED RATS - ANALYSIS OF MOTOR AND COGNITIVE EFFECTS AND MUSCARINIC-INDUCED STRIATAL DOPAMINE RELEASE

Nimodipine is a calcium channel blocker reported to have beneficial ef fects on treatment of ischemic damage as well as the potential for ret arding aspects of brain and behavioral aging when provided chronically to rats. We treated aged male F-344 rats (24 months) with nimodipine in SC pellets in the following doses: 0 (controls), 20 mg (low-dose), or 40 mg (high-dose) replenished after 6 weeks. After 3 months of trea tment, surviving rats and a group of young controls (6 months) were te sted in a behavioral battery involving exploratory activity in an open field and in a runwheel cage as well as motor abilities required for remaining on an inclined screen, suspended from a wire, and balanced o n a rotorod. Rats were also pretrained for one-way active avoidance in a straight runway before being trained in a 14-unit T maze. During 20 trials rats were required to negotiate each of 5 maze segments within 10s to avoid foot shock (0.8 mA). Nimodipine treatment produced no si gnificant effects on body weight, food intake, or survival of aged rat s. Analysis of behavioral results indicated significant age-related de cline in performance of all tasks except in open-field behavior. Nimod ipine treatment had no significant effects on behavioral performance o f aged rats except in maze learning. Rats on the high-dose regimen per formed significantly better than aged controls in the maze. The result s indicate that chronic nimodipine treatment of aged rats had no toxic effects and might be beneficial for preventing age-related decline in learning performance.