The objective of this project is to characterize changes in the properties of catecholaminergic nerves in the brains of male and female rats which occur during the aging process, and to relate these changes to alterations in the reproductive and endocrinological status of these animals. Microchemical techniques will be employed to measure steady state concentrations and the rates of synthesis and turnover of norepinephrine and dopamine in specific brain regions of young (3-5 months), middle-aged (14-16 months) and aged (22-26 months) rats. The estrous cycle will be characterized in female rats and the serum concentrations of prolactin, luteinizing hormone and testosterone or progesterone will be determined in both males and females. The endocrinological and neurochemical responses of the animals to acute and chronic administration of dopamine agonists and antagonists, and to altered endocrine states (castration, administration of estrogens, progesterone or testosterone) will also be determined. Efforts will be made to develop animal models which may advance our understanding of some of the neurochemical and neuroendocrinological features of the aging process. These will include studies in male and female rats which have been treated with 6-hydroxydopamine in order to partially destroy central catecholaminergic nerves, and in females treated as neonates with testosterone in order to produce the early development of constant estrus.
