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.
