We propose to investigate the interrelationships of hormones, neurotransmitters and their receptors with metabolic state and normal development of the brain and other organs; and to study the role of these neurotransmitters and hormones in mediating perturbations in the development and metabolism caused by psychoactive drugs and various stress conditions. Neurotransmitter and hormone changes will be related to concurrent alterations in specific cellular receptor and metabolic parameters in brain, heart, liver, kidney and blood vessels i.e. primarily adrenergic receptors and polyamine metabolism.
Our aim i s to elucidate the role the central and peripheral nervous systems play in regulating hormone release, cell metabolism and physiologic function and in mediating the effects of drugs, hormones and environmental influencs on organ function in normal and different disease states. Our basic experimental approach utilizes assessment of multiple physiological and biochemical parameters in developing organ systems as indices of altered functional maturation of those systems caused by behavioral """"""""stress"""""""" or psychopharmacologic agents. Specific behavioral paradigm include maternal deprivation, immobilization and shaker stress. Other studies include the maturation of neurotransmitter and neurotrophic polypeptide regulation of growth hormone and ACTH release in the developing neonate and pharmacologic models of chronic sympathetic stimulation i.e. norepinephrine, epinephrine, phenylephrine and isoproterenol and/or chronic glucocorticoid stimulation i.e. corticosterone, dexamethasone, ACTH and CRF.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH013688-21
Application #
3374627
Study Section
(BPNA)
Project Start
1976-09-01
Project End
1988-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
21
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Duke University
Department
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
Bartolome, J V; Wang, S; Schanberg, S M et al. (1999) Involvement of c-myc and max in CNS beta-endorphin modulation of hepatic ornithine decarboxylase responsiveness to insulin in rat pups. Life Sci 64:PL87-91
Bartolome, J V; Johnston, J G; Schanberg, S M (1994) The inhibition of liver ornithine decarboxylase expression in neonatal rats by maternal separation or CNS beta-endorphin is independent of the pituitary. Life Sci 54:679-86
Borowsky, B; Kuhn, C M (1991) Monoamine mediation of cocaine-induced hypothalamo-pituitary-adrenal activation. J Pharmacol Exp Ther 256:204-10
Bartolome, J V; Bartolome, M B; Lorber, B A et al. (1991) Effects of central administration of beta-endorphin on brain and liver DNA synthesis in preweanling rats. Neuroscience 40:289-94
Johnson, M D; McMillian, M K; Schanberg, S M (1991) Alterations in cardiovascular responsiveness and adrenoceptor binding during catecholamine infusion hypertension in rats. Proc Soc Exp Biol Med 197:67-73
Greer, N L; Bartolome, J V; Schanberg, S M (1991) Further evidence for the hypothesis that beta-endorphin mediates maternal deprivation effects. Life Sci 48:643-8
Owens, M J; Bartolome, J; Schanberg, S M et al. (1990) Corticotropin-releasing factor concentrations exhibit an apparent diurnal rhythm in hypothalamic and extrahypothalamic brain regions: differential sensitivity to corticosterone. Neuroendocrinology 52:626-31
Kuhn, C M; Pauk, J; Schanberg, S M (1990) Endocrine responses to mother-infant separation in developing rats. Dev Psychobiol 23:395-410
Bartolome, J V; Bartolome, M B; Harris, E B et al. (1989) Regulation of insulin and glucose plasma levels by central nervous system beta-endorphin in preweanling rats. Endocrinology 124:2153-8
Gelman, J; Bartolome, J V; Jenkins, S et al. (1987) Reduced cell death in skin flaps in rats treated with difluoromethylornithine. FASEB J 1:474-7

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