Effects of Aging and Morphine Administration on Calmodulin and Calmodulin-Regulated Enzymes in Striata of Mice

Abstract
Male ICR mice, young (25 days old), mature (3 mo. old), and old (22 mo.), were injected with morphine sulfate (10 mg/kg, s.c.) or were implanted with morphine pellets (75 mg). Controls received saline injections or placebo pellets. One hour after injections and 72 h after pellet implantations, the mice were decapitated and striatal regions were removed for the following analyses: calmodulin (CaM) levels via radioimmunoassay and activities of cyclic nucleotide phosphodiesterases, adenylate and guanylate cyclases, and Ca2+,Mg2+-ATPase. Acute morphine treatment produced the following: increases in calmodulin levels in the young and old mice while having no effect on mature levels; increases in activities of guanylate cyclase of mature mice while decreasing those of the old mice; no effects on activity of adenylate cyclase; decreased activity of cAMP-phosphodiesterase in young mice only; and decreased activity of Ca2+,Mg2+-ATPase in the old mice only. The only changes found in striata from morphine-tolerant mice when compared with age-matched controls were elevations in cGMP-phosphodiesterase activities in all 3 age groups. Differences in control values of the 3 age groups were as follows: CaM levels, mature > old > young; Ca2+,Mg2+ -ATPase activity, old > mature-young. The results indicate age-induced changes in cellular regulation and biochemical responses to morphine.