The aging process in mammalian species includes changes in neuroendocrine function which result in a loss of female reproductive function. The onset of acyclicity and infertility found with general senescence appears to be a consequence of the age-related loss of hypothalamic-pituitary-ovarian function. The neuroendocrine events suggested as critical factors responsible for the loss of estrous cyclicity in the female rat include alteration of estrogen receptors as well as changes in the biogenic amine neurotransmitters serotonin (5-HT) and norepinephrine (NE) in the central nervous system. The objective of this research is to increase our understanding of the cellular physiological events in the brain which mediate these changes in reproductive function and, thereby, add to our general knowledge of neuroendocrine aging processes. We propose to test the hypothesis that changes in sensitivity to 5-HT and NE are important in aging and the development of acyclicity in the female rat by evaluating the direct actions of these neurotransmitters on the cell firing of serotonin-containing cells in the dorsal raphe nucleus and norepinephrine-containing cells in locus coeruleus. Extracellular single unit recording techniques and microiontophoretic drug application will be utilized to investigate these transmitter-specific cell groups in young and middle-aged female rats. We also propose to evaluate whether estrogen can directly alter the firing of these two cell groups and, in turn, modulate neuronal responses to 5-HT and NE at the cellular level with respect to aging. In addition, an in vitro slice preparation of the dorsal raphe nucleus will be utilized to facilitate intracellular recordings to identify the ionic mechanism(s) by which estrogen and biogenic amines may mediate the decline of reproductive function in the female rat.
