The overall objective of the research is an identification of the neurophysiological mechanisms by which estradiol and progesterone, operating through specific neuroanatomical sites, regulate the function of behavior-controlling midbrain and hypothalamic neurons. The model neurobehavioral system for the proposed research is the facilitation of lordosis, a sexually- receptive postural response to lumbosacral tactile stimulation, by effects of estradiol and progesterone on the brain in female golden hamsters. Previous research has shown the lordosis- inducing effects of estradiol to be mediated principally through ventromedial hypothalamic neurons. Progesterone, in contrast, has more widespread critical sites of action, including the midbrain as well as the hypothalamus. In addition, a variety of evidence indicates that progesterone operates through multiple mechanisms of action in addition to multiple neuroanatomical sites. Previous research in this program has identified the principal, lordosis-related effects on midbrain and hypothalamic neurons, of whole brain exposure to estradiol and progesterone. The proposed research will entail studies in freely-behaving hamsters involving: (1) sequential, localized implantation of estradiol and progesterone in the ventromedial hypothalamus and (2) chronic or acute implantation of progesterone in the dorsal or ventral midbrain. Behavior-related single neuron activity will be recorded at the implant sites and from spatially separate, but functionally related brain sites, as the combined behavioral effects of the hormone implants and systemically-administered estradiol or progesterone emerge. The specific regional actions of these hormones which underlie their lordosis-inducing effect will thus be identified. Health-related significance of the proposed research lies in the fact that estrogens and progestins, in natural and synthetic variations, are of great clinical importance, with the potential for greater neurological and behavioral applications. These hormones play critical roles in human brain and behavioral development, influence adult cognitive functioning and can exacerbate or ameliorate certain neurological diseases. It is anticipated that the therapeutic potential of these hormones could be better exploited and their pathological influences better managed, once a more complete basic understanding of their neural actions has been obtained.
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