In response to a stressor, activation of endocrine, autonomic, and behavioral systems occurs presumably to enhance the organism's ability to endure and survive the stress. Behavioral and psychological factors modulate the behavioral and psycholoigcal impact of exposure to a stressor. The ability to control one's exposure to aversive events is especially important. Although the behavioral impact of the control dimension has been studied extensively, few studies have explored effects on autonomic function and none have examined effects on cardiovascular system (CVS) function. Neither effects of control over an aversive event on brain neuropeptides nor the potential role of these systems in mediating the behavioral, autonomic, and CVS sequelae of aversive events differing in controllability has been explored. Our hypothesis is that the lack of control over aversive events will lead to an enhanced autonomic and CVS response and that these effects may in part be mediated by specific brain neuropeptide systems. Our objective is to determine if (i) control versus lack of control over the same aversive events is associated with differential autonomic activation and CVS response, (ii) control versus lack of control over the same aversive events is associated with differential effects on brain cortiocotropin releasing factor (CRF), vasopressin (VP), and angiotension II (AII) and in peripheral VP and AII systems, and (iii) alteration of these neuropeptide systems in the brain affects the behavioral, autonomic, and CVS outcomes associated with the lack of control over aversive events. To study (i), we will measure plasma nonrepinephrine and epinephrine and monitor blood pressure and heart rate in rats that have received physically identical electric shocks, differing only in controllability. The full timecourse of these potential changes will be explored. To study (ii), we will measure CRD, VP, and AII immunoreactivitiy using radioimmunoassay in hypothalamus, cortex, hippoampus, and brainstem, and we will measure AII and VP from plasma in rats that have received physically identical electric shocks, differing only in controllability. To study (iii), function of brain peptide systems will be altered by intracerebroventricular administration of peptide agonists and antagonists. The impact of these manipulations on the behavioral, peripheral catecholamine, and cardiovascular changes normally produced by uncontrollable and controllable aversive events will be assessed.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL035143-03
Application #
3348773
Study Section
(SRC)
Project Start
1985-09-30
Project End
1988-09-29
Budget Start
1987-09-30
Budget End
1988-09-29
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Takahashi, L K; Kalin, N H; Baker, E W (1990) Corticotropin-releasing factor antagonist attenuates defensive-withdrawal behavior elicited by odors of stressed conspecifics. Behav Neurosci 104:386-9
Takahashi, L K; Kalin, N H; Vanden Burgt, J A et al. (1989) Corticotropin-releasing factor modulates defensive-withdrawal and exploratory behavior in rats. Behav Neurosci 103:648-54
Carnes, M; Kalin, N H; Lent, S J et al. (1988) Pulsatile ACTH secretion: variation with time of day and relationship to cortisol. Peptides 9:325-31
Kalin, N H; Sherman, J E; Takahashi, L K (1988) Antagonism of endogenous CRH systems attenuates stress-induced freezing behavior in rats. Brain Res 457:130-5
Takahashi, L K; Kalin, N H; Barksdale, C M et al. (1988) Stressor controllability during pregnancy influences pituitary-adrenal hormone concentrations and analgesic responsiveness in offspring. Physiol Behav 42:323-9
Sherman, J E; Kalin, N H (1988) ICV-CRH alters stress-induced freezing behavior without affecting pain sensitivity. Pharmacol Biochem Behav 30:801-7
Sherman, J E; Kalin, N H (1987) The effects of ICV-CRH on novelty-induced behavior. Pharmacol Biochem Behav 26:699-703
Carnes, M; Barksdale, C M; Kalin, N H et al. (1987) Effects of dexamethasone on central and peripheral ACTH systems in the rat. Neuroendocrinology 45:160-4
Sherman, J E; Kalin, N H (1986) ICV-CRH potently affects behavior without altering antinociceptive responding. Life Sci 39:433-41