The general purpose of this proposal is to analyze some of the complex interactions which exist between neurotransmitter and peptidergic neurons within the hypothalamus. To learn more of how axons from the locus coeruleus (LC) and the medullary Al and A2 regions projects to hypothalamic regions containing LHRH neurons, specific transections and lesions within the hypothalamus will be made. Recent studies show that all LC stimulatory NE axons decussate to reach contralateral LHRH neurons. In these and other studies, anesthetized, estrogen-treated ovariectomized rats will have their medial preoptic nucleus (MPN) electrochemically stimulated (ECS) and, thereafter, the LC, A1 or A2 cell groups will be electrically stimulated (ES). Such LC or A1 ES amplifies LH release. Other studies will examine whether neuroexcitant drugs (e.g. 3-isobutyl-methylxanthine) active NE secretion when microinfused into LC or A1 of unanesthetized rats. The paragigantocellularis nucleus (PGC) in the ventrolateral medulla regulates LC neuronal activity, presumably by releasing excitatory amino acids (EAA). ES of PGC on will be performed to determine if such stimuli increase hypothalamic NE secretion. Other studies will evaluate whether the microinfusion of EAA into LC has a similar excitatory effect in releasing NE and LHRH/LH. Since LHRH neurons may be activated only when specifically coded noradrenergic signals are presented, the parameters of LC or A1 ES will be varied to study how such stimuli affect LHRH neuronal activity. As NE may act via a GABA interneuron, the role of hypothalamic GABA neurons in the regulation of NE-induced LHRH release will be examined. The role of the opiate system in modulating NE secretion also will be studied. In these experiments, specific agonists or antagonists of GABA or opiate receptors will be placed into selective hypothalamic, mid or hindbrain regions and their effects on NE and LHRH secretion following mid or hindbrain ES will be assessed. Changed in NE and LHRH secretion after LC, A1 and A2 ES will be evaluated by HPLC and RIA in dialysates obtained from microdialysis probes placed into specific hypothalamic areas and the pituitary gland. The serotonin (5-HT) system also is to be studied with particular emphasis on how 5-HT and NE interact to excite or inhibit LHRH neuronal activity. Finally, NE and 5-HT interactions with LHRH neurons in androgen-sterilized and male rats are to be examined. These studies should provide important fundamental new information on how the neuroendocrine brain functions to evoke preovulatory gonadotropin surges and ovulation.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD002138-29
Application #
3310152
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1978-09-01
Project End
1993-05-31
Budget Start
1990-06-01
Budget End
1991-05-31
Support Year
29
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Type
Schools of Medicine
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201
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Darlington, D N; Jones, R O; Magnuson, T A et al. (1995) Role of intestinal fluid in restitution of blood volume and plasma protein after hemorrhage in awake rats. Am J Physiol 268:R715-22
He, J R; Molnar, J; Barraclough, C A (1994) Evidence that amplification of norepinephrine-induced LH release by morphine is indirectly due to suppression of tuberoinfundibular dopamine secretion. Brain Res 653:1-8
Molnar, J; He, J R; Barraclough, C A (1994) Effect of morphine on hypothalamic tyrosine hydroxylase mRNA levels in dopaminergic neurons and on preoptic DOPAC levels measured by microdialysis. Brain Res Mol Brain Res 22:97-106
Barraclough, C A (1994) Neurotransmitter regulation of luteinizing hormone-releasing hormone neuronal function. Acta Biol Hung 45:189-206
Liaw, J J; Barraclough, C A (1993) N-methyl-D,L-aspartic acid differentially affects LH release and LHRH mRNA levels in estrogen-treated ovariectomized control and androgen-sterilized rats. Brain Res Mol Brain Res 17:112-8
Liaw, J J; Barraclough, C A (1993) Pituitary gland responsiveness to LHRH and LHRH neuronal responsiveness to excitatory stimuli are severely impaired in female rats treated neonatally with high doses of androgen. Brain Res 607:233-40
He, J R; Molnar, J; Barraclough, C A (1993) Morphine amplifies norepinephrine (NE)-induced LH release but blocks NE-stimulated increases in LHRH mRNA levels: comparison of responses obtained in ovariectomized, estrogen-treated normal and androgen-sterilized rats. Brain Res Mol Brain Res 20:71-8
Barraclough, C A (1992) Neural control of the synthesis and release of luteinizing hormone-releasing hormone. Ciba Found Symp 168:233-46;discussion 246-51
Darlington, D N; Barraclough, C A; Gann, D S (1992) Hypotensive hemorrhage elevates corticotropin-releasing hormone messenger ribonucleic acid (mRNA) but not vasopressin mRNA in the rat hypothalamus. Endocrinology 130:1281-8

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