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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS013748-17
Application #
3395305
Study Section
Biopsychology Study Section (BPO)
Project Start
1978-09-30
Project End
1994-08-31
Budget Start
1992-09-01
Budget End
1993-08-31
Support Year
17
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Wyoming
Department
Type
Schools of Arts and Sciences
DUNS #
069690956
City
Laramie
State
WY
Country
United States
Zip Code
82071
Rose, J D (2000) Corticosteroid actions from neuronal membrane to behavior: neurophysiological mechanisms underlying rapid behavioral effects of corticosterone. Biochem Cell Biol 78:307-15
Lowry, C A; Rose, J D; Moore, F L (1996) Corticotropin-releasing factor enhances locomotion and medullary neuronal firing in an amphibian. Horm Behav 30:50-9
Rose, J D; Kinnaird, J R; Moore, F L (1995) Neurophysiological effects of vasotocin and corticosterone on medullary neurons: implications for hormonal control of amphibian courtship behavior. Neuroendocrinology 62:406-17
Orchinik, M; Moore, F L; Rose, J D (1994) Mechanistic and functional studies of rapid corticosteroid actions. Ann N Y Acad Sci 746:101-12;discussion 112-4
Rose, J D; Flynn, F W (1993) Lordosis response components can be elicited in decerebrate rats by combined flank and cervix stimulation. Physiol Behav 54:357-61
Rose, J D; Moore, F L; Orchinik, M (1993) Rapid neurophysiological effects of corticosterone on medullary neurons: relationship to stress-induced suppression of courtship clasping in an amphibian. Neuroendocrinology 57:815-24
Rose, J D (1990) Forebrain influences on brainstem and spinal mechanisms of copulatory behavior: a current perspective on Frank Beach's contribution. Neurosci Biobehav Rev 14:207-15
Havens, M D; Rose, J D (1988) Estrogen-dependent and estrogen-independent effects of progesterone on the electrophysiological excitability of dorsal midbrain neurons in golden hamsters. Neuroendocrinology 48:120-9
Rose, J D; Havens, M D (1986) Lordosis-disrupting tectal lesions alter midbrain unit somatosensory responsiveness in hamsters. Brain Res Bull 16:39-45
Mackay-Sim, A; Rose, J D (1986) Removal of the vomeronasal organ impairs lordosis in female hamsters: effect is reversed by luteinising hormone-releasing hormone. Neuroendocrinology 42:489-93

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