Methadone in brain and its effects on locomotor activity of young and aged mice

Plasma and brain levels of methadone produced by subcutaneous injections of the chloride salt (7.5, 15.0 or 22.5 mg/kg) and resultant changes in locomotor activity were determined in young (6-8 months) and aged (30-32 months) C57BL/6J mice. Methadone elevated locomotor activity of young and aged mice above control levels to about the same extent. The degree of activity elevation was inversely related to dose for both age groups, however, the reduction in stimulation with increasing dose was greater for young than aged mice; and only young mice exhibited a significant biphasic response to the high drug dose. Although the behavioral results suggest that aged mice were less responsive than young mice to methadone, brain concentrations of the drug were higher in aged than young mice by approximately one hour after injection. The age difference noted in brain concentration was not observed for plasma levels of methadone; hence cannot be accounted for by reduced drug metabolism in aged mice. The results of this study indicate that compared to young adults, aged mice are less responsive behaviorally to methadone despite higher brain concentrations of the drug.