Serotonin pharmacodynamics in hypothalamic tissues from young and old female rats

The purpose of this study was to determine the effects of aging on serotonin (5-HT) pharmacodynamics in rostral hypothalamic tissue of female rats. Monoamine oxidase (MAO) activity was greater in old (19 months old) than in young (3 months old) animals. This difference resulted from a higher Vmax for hypothalamic MAO from old rats, whereas Km's were comparable in both age groups. These enzymatic changes were accompanied by altered uptake and release of [3H]5-HT. Although [3H]5-HT uptake was not different at equilibrium between groups, the equilibrium state was achieved more slowly by hypothalamic tissue from old rats. Basal and potassium-stimulated efflux of [3H]5-HT was significantly greater in old rats compared with young ones and these differences remained during multiple depolarizations. The findings of this study suggest that synaptic levels of hypothalamic 5-HT increase with age. Since pharmacological simulation of this condition in young rats produces physiologic dysfunction, the spontaneous changes that occur in hypothalamic 5-HT pharmacodynamics during aging have the potential to promote senescence.