This is a competing continuation application for grant support of research exploring the role of catecholaminergic systems in the control of the adaptive physiological and behavioral responses to stress. It has long been known that the sympathoadrenal system plays a critical role in maintaining homeostasis during stress. More recent work has suggested that central dopaminergic and noradrenergic neurons have a parallel role in the mediation of the appropriate behavioral responses to stimulation. For the past 12 years, we have been examining the effects of stress on the biosynthesis of catecholamines (CAs), the relation between alterations in CA biosynthesis and CA release, and the functional impact of those released CAs, both in the periphery and in the brain. During the next 5 years, we hope to determine each of the following: (a) Whether the increase in tyrosine hydroxylase (TH) activity that has been observed in the sympathetic nerves and adrenal glands of rats exposed to chronic cold stress or insulin- induced hypoglycemia is associated with an increased capacity for CA release, and if so, whether this enhanced release results in physiologically significant effects on cardiovascular function. (b) Whether acute stress activates TH in the sympathoadrenal system of rats that previously had been exposed to chronic stress, and if so, whether this is associated with an enhanced capacity for CA release. (c) Whether chronic insulin-induced hypoglycemia increases the activity of phenylethanolamine N-methyltransferase (PNMT) in the adrenal medulla of rats, and if so, whether this is associated with an enhanced capacity for epinephrine secretion. (d) Whether chronic stress is associated with an increase in the amount of messenger RNA for TH and PNMT in the adrenal medulla of rats and if so, whether the time course of this effect parallels the observed changes in enzyme activity. (e) Whether alterations in TH mRNA levels can be linked to increased activity of preganglionic sympathetic input to the adrenal medulla. (f) Whether activation and induction of TH occurs in cental noradrenergic neurons when rats are exposed to cold stress or insulin-induced hypoglycemia and if so, whether there are parallel effects of stress on enzyme gene expression.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH029670-14
Application #
3375126
Study Section
Neurosciences Research Review Committee (BPN)
Project Start
1977-06-01
Project End
1992-11-30
Budget Start
1991-02-01
Budget End
1991-11-30
Support Year
14
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
Schools of Arts and Sciences
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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Vollmer, R R; Baruchin, A; Kolibal-Pegher, S S et al. (1992) Selective activation of norepinephrine- and epinephrine-secreting chromaffin cells in rat adrenal medulla. Am J Physiol 263:R716-21
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