Effects of aging and chronic nimodipine on hippocampal binding of [3H]CGS 19755.
Previous studies have suggested that aging is associated with impaired behavioral performance and with decrements of N-methyl-D-aspartate (NMDA) receptors in the rat hippo-campus. Other studies have indicated that chronic treatment with nimodipine, a Ca2+ channel antagonist, prevents the age-related decline in performance by rats in behavioral tasks. Therefore, we tested whether nimodipine altered binding of [3H]CGS 19755 to hippocampal NMDA receptors in rats whose performance on a 14-unit T maze had been tested previously (14). No significant age difference was observed in [3H]CGS 19755 binding in hippocampi from old Fischer-344 rats (27 months) as compared with mature but not senescent rats (9 months); however, old rats that received chronic treatment with a low dose of nimodipine (20 mg pellets implanted subcutaneously twice during 70 days of treatment) showed higher levels of binding. A high dose of nimodipine (40 mg pellets implanted by the same route and at the same times as the low dose) was without effect on [3H]CGS 19755 binding, although aged rats given this treatment performed better in the maze than rats that received no nimodipine or the low dose. In a second experiment comparing hippocampi of young (4 months) and old (24 months) rats, saturation studies confirmed the lack of an age difference in [3H]CGS 19755 binding. The findings suggest that neither the age-related decline in maze performance nor the enhancement of behavior by nimodipine depend upon changes in hippocampal NMDA receptors.
Kusztos
R D
RD
Neuroimaging and Drug Action Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
Ingram
D K
DK
Spangler
E L
EL
London
E D
ED
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D009553:Nimodipine / Q000494:pharmacology*; D010875:Pipecolic Acids / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344
D018691:Excitatory Amino Acid Antagonists; D010875:Pipecolic Acids; C053672:selfotel; D009553:Nimodipine