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 effects on treatment of ischemic damage as well as the potential for retarding 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 treatment, surviving rats and a group of young controls (6 months) were tested 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 on 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 10 s to avoid foot shock (0.8 mA). Nimodipine treatment produced no significant effects on body weight, food intake, or survival of aged rats. Analysis of behavioral results indicated significant age-related decline in performance of all tasks except in open-field behavior. Nimodipine treatment had no significant effects on behavioral performance of aged rats except in maze learning. Rats on the high-dose regimen performed significantly better than aged controls in the maze. The results indicate that chronic nimodipine treatment of aged rats had no toxic effects and might be beneficial for preventing age-related decline in learning performance.
Ingram
D K
DK
Molecular Physiology and Genetics Section, Nathan W. Shock Laboratories, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224.
Joseph
J A
JA
Spangler
E L
EL
Roberts
D
D
Hengemihle
J
J
Fanelli
R J
RJ
D000375:Aging / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D004435:Eating / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009553:Nimodipine / Q000097:blood / Q000494:pharmacology*; D010095:Oxotremorine / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology*; D004856:Postural Balance / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344
D010277:Parasympathomimetics; D009553:Nimodipine; D010095:Oxotremorine; D004298:Dopamine