In this proposal, I have outlined a program of research which focuses on homeostatic regulation of the sympathetic nervous system of laboratory rats during chronic exposure to stressful stimulation. The stress concept was first introduced by Hans Selye nearly 50 years ago. In spite of extensive research on the stress responses of animals and humans over the years, there remains a glaring absence of a soundly developed and widely accepted theoretical framework for this field of research. In this proposal, several experiments are described which will clarify the underlying adaptive responses of the sympathetic nervous system to acute versus chronic exposure to stressful stimulation. In the first experiment, adult male laboratory rats will be stressed 30 minutes per day for 0, 1, 7, 14, or 28 consecutive days in one of the following conditions: immobilization (IM), exposure to intermittent, inescapable footshock (FS), or immersion in 18 degrees C water (CI). To control for the element of predictability, another group of rats will be exposed randomly to 1 of the 3 stressors for 7, 14, or 28 consecutive days. Plasma levels of norepinephrine and epinephrine will be measured in blood samples taken before, during, and after stressful stimulation as an index of sympathetic-adrenal medullary activity. In addition, the effects of these stress regimens on catecholamine biosynthetic enzyme activities and catecholamine content of several sympathetically innervated tissues will be quantified. In a second series of """"""""Cross-over"""""""" experiments, rats will be stressed chronically in one condition and then acutely in another (i.e. chronic IM-acute FS; chronic FS-acute CI; chronic CI-acute IM) to examine the sympathetic responsiveness of a chronically stressed animal to a novel stressor. The results of this research will provide an extensive empirical base for refining and extending the conceptualization of stress. In addition, it will serve as a foundation for directing the research efforts of my laboratory toward the study of central neuronal adaptations to stressful stimulation in laboratory animals. These findings will be of direct relevance to several stress-related disorders in humans, including peptic ulcer disease, hypertension, depression and coronary artery disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH039970-01
Application #
3377796
Study Section
(BPNB)
Project Start
1985-09-01
Project End
1988-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Virginia
Department
Type
Schools of Arts and Sciences
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
McCarty, R; Eisen, G; Bartholow, C L (1991) Plasma catecholamine responses to acute motion stress in laboratory rats. Physiol Behav 49:653-6
Konarska, M; Stewart, R E; McCarty, R (1990) Habituation and sensitization of plasma catecholamine responses to chronic intermittent stress: effects of stressor intensity. Physiol Behav 47:647-52
Konarska, M; Stewart, R E; McCarty, R (1990) Predictability of chronic intermittent stress: effects on sympathetic-adrenal medullary responses of laboratory rats. Behav Neural Biol 53:231-43
Konarska, M; Stewart, R E; McCarty, R (1989) Sensitization of sympathetic-adrenal medullary responses to a novel stressor in chronically stressed laboratory rats. Physiol Behav 46:129-35
Lee, J H; Konarska, M; McCarty, R (1989) Physiological responses to acute stress in alloxan and streptozotocin diabetic rats. Physiol Behav 45:483-9
Konarska, M; Stewart, R E; McCarty, R (1989) Habituation of sympathetic-adrenal medullary responses following exposure to chronic intermittent stress. Physiol Behav 45:255-61
Natelson, B H; Ottenweller, J E; Cook, J A et al. (1988) Effect of stressor intensity on habituation of the adrenocortical stress response. Physiol Behav 43:41-6
McCarty, R; Horwatt, K; Konarska, M (1988) Chronic stress and sympathetic-adrenal medullary responsiveness. Soc Sci Med 26:333-41