Role of the bed nucleus of the stria terminalis in the cardiovascular responses to acute restraint stress in rats

The aim of this work was to test the hypothesis that the bed nucleus of the stria terminalis (BST) and noradrenergic neurotransmission therein mediate cardiovascular responses to acute restraint stress in rats. Bilateral microinjection of the non-specific synaptic blocker CoCl(2) (0.1 nmol/100 nl) into the BST enhanced the heart rate (HR) increase associated with acute restraint without affecting the blood pressure increase, indicating that synapses within the BST influence restraint-evoked HR changes. BST pretreatment with the selective alpha(1)-adrenoceptor antagonist WB4101 (15 nmol/100 nl) caused similar effects to cobalt, indicating that local noradrenergic neurotransmission mediates the BST inhibitory influence on restraint-related HR responses. BST treatment with equimolar doses of the alpha(2)-adrenoceptor antagonist RX821002 or the beta-adrenoceptor antagonist propranolol did not affect restraint-related cardiovascular responses, reinforcing the inference that alpha(1)-adrenoceptors mediate the BST-related inhibitory influence on HR responses. Microinjection of WB4101 into the BST of rats pretreated intravenously with the anticholinergic drug homatropine methyl bromide (0.2 mg/kg) did not affect restraint-related cardiovascular responses, indicating that the inhibitory influence of the BST on the restraint-evoked HR increase could be related to an increase in parasympathetic activity. Thus, our results suggest an inhibitory influence of the BST on the HR increase evoked by restraint stress, and that this is mediated by local alpha(1)-adrenoceptors. The results also indicate that such an inhibitory influence is a result of parasympathetic activation.     

Peripheral oxytocin administration buffers autonomic but not behavioral responses to environmental stressors in isolated prairie voles

Negative social experiences such as social stressors and isolation influence mental and physical illnesses, including affective disorders and heart disease. Studies focused on socially monogamous prairie voles can provide insight into neurobiological systems that underlie the consequences of negative social interactions. Female prairie voles were exposed to 28 days of social isolation or pairing with a female sibling (control). Voles were administered daily oxytocin [20 μg/50 μl, subcutaneous (sc)] or saline vehicle (50 μl, sc) for 14 days and exposed to two behavioral stressors [elevated plus maze (EPM) and resident-intruder test]. Brain tissue was collected for analysis of central peptide levels in the hypothalamic paraventricular nucleus (PVN). Isolation produced autonomic changes [increased heart rate (HR) and decreased HR variability) during both acute stressors and increased anxiety behaviors in the EPM. Oxytocin injection prevented the autonomic consequences of the acute stressors in isolated prairie voles, but did not affect the behaviors tested under the present conditions. Oxytocin had no effect on the behavioral or autonomic responsiveness in paired prairie voles. Oxytocin injection may exert a beneficial effect on autonomic responses to stressors in isolated animals through increasing the number of oxytocin-containing neurons and decreasing the number of corticotropin-releasing hormone-containing neurons in the PVN. Oxytocinergic mechanisms may serve to compensate for autonomic responses associated with chronic isolation and exposure to both social and non-social acute stressors.     

Motivational Systems and Stress-Related Cardiovascular Reactivity

This study examined the relation of motivational systems to patterns of autonomic responses to stress. Specifically, we examined patterns of physiological response resulting from differential activation of motivational systems for behavioral approach and behavioral inhibition. We also examined the relation of these motivational systems to threat and challenge responses to potential stress. Self-report, cardiac measures (i.e., pre-injection period, or PEP, and heart rate, or HR), and blood pressure (i.e., systolic blood pressure, or SBP, and diastolic blood pressure, or DBP) measures reliably distinguished between an experimental condition facilitating behavioral approach and an experimental condition facilitating coactivation of behavioral approach and behavioral inhibition systems. Vascular (e.g., total peripheral resistance, or TPR) and electrodermal (e.g., electrodermal response, or EDR) measures, however, did not vary by condition. We discuss the results in relation to other research on motivational factors as they relate to stress and cardiovascular reactivity.     

A mechanical method for changing heart rate and blood pressure

The investigation of afferent cardiovascular influences upon central nervous processes needs a methodology which allows for independent and systematic manipulation of circulatory processes. By mechanical manipulation of posture (tilt table, orthostasis) and compression of lower body parts (by anti-G-suit) reliable changes in heart rate and blood pressure can be induced. In fourty subjects (study 1) it could be shown that sustained (30 min.) changes in heart rate (e.g. orthostatic tachycardia, decrease of heart rate during compression) and mean arterial blood pressure (increase during orthostasis with and without compression) occur. Although changes in heart rate could be achieved irregardless of whether the venous "pooling" was suppressed by an air- or water-filled pressure suit, the pressor effect did differ quite considerably. In fourty-four subjects (study 2) it could be demonstrated that only by means of an water-filled suit further increases in mean arterial blood pressure could be evoked during orthostasis. Changes in hemodynamic also lead to changes in sympatho-vagal control of cardiac activity. In study 3 (ten subjects) it could be shown, that orthostasis mainly evokes alterations in sympathetic activity whereas lower body compression leads to additional increases of vagal activity and respiratory sinus arrhythmia during orthostasis.     

Gender differences in cardiovascular and hypothalamic-pituitary-adrenal axis responses to psychological stress in healthy older adult men and women

Gender differences in the neuroendocrine and cardiovascular response to psychological stress may contribute to the gender differences in the prevalence of diseases associated with hypothalamic-pituitary-adrenal (HPA) axis reactivity such as cardiovascular disease (CVD), diabetes and hypertension. We measured plasma ACTH, cortisol, heart rate (HR), and blood pressure (BP) responses in 8 men and 8 women (55-75 years) exposed to the Matt Stress Reactivity Protocol (MSRP), a psychological challenge. The MSRP elicited significant increases in HR, systolic-, and diastolic BP, ACTH and cortisol (all p<0.01). Men had significantly greater cortisol and diastolic BP responses compared to women (p<0.05). Additionally, a positive correlation between the ACTH and cortisol responses was only found in the males (r=0.71, p<0.05). There were no group differences in HR, systolic BP, or ACTH responses. We conclude, that among older adults, men respond to psychological stress with greater increases in cortisol, compared to women. This greater activation of the HPA axis could translate into an elevated risk for CVD, diabetes and hypertension and may be related to the higher prevalence of these diseases in males. Gender differences in brain structures and/or cognitive processes may be responsible for these sexually dimorphic stress responses.     

Human visual evoked responses are related to heart rate.

The purpose of the present experiment was to determine the relation between changes in heart rate and averaged evoked potentials. Sixteen male subjects with variable heart rates received 50 flashes of light during fast heart beats, 50 during slow heart beats, and 50 during midrange heart rate level. Evoked responses were recorded from the scalp overlying the right and left occipital lobes. Heart rate, respiration, eye movements, and cephalic blood flow were also recorded. The results indicated that spontaneous changes in heart rate are related to changes in visual evoked responses and that this relation differs for the two cerebral hemispheres. Furthermore, cephalic pulse amplitude was largest following slow heart beats and smallest following fast heart beats, which suggests that changes in heart rate are related to changes in cerebrovascular as well as electrocortical activity. The results are discussed in terms of formulations derived from behavioral studies regarding the relation between cardiovascular activity and attentional processes.     

Heart rate changes accompanying jaw movement Pavlovian conditioning in rabbits: Concomitant blood pressure adjustments and effects of peripheral autonomic blockade

Two experiments were conducted to ascertain the cardiovascular accompaniments of differential Pavlovian jaw movement (JM) conditioning. The first examined the blood pressure (BP) changes that accompany the tachycardiac conditioned responses (CRs) associated with JM conditioning. The BP response in all instances consisted of a depressor response that was greater to the reinforced CS+ than CS-, although the magnitude of the CR was quite small. The second experiment determined the effects of peripheral autonomic antagonists on the cardiac accelerations associated with JM conditioning. It was found that the peripheral vagal antagonist methyl scopolamine completely abolished responses to both CS+ and CS-, whereas atenolol, a beta adrenergic antagonist, augmented the response, compared to saline control injections. The JM responses were also affected by the autonomic blockades, with minimal responding occurring in the scopolamine group but slightly more JM CRs in the atenolol group, compared to saline control animals. These results suggest that the major cardiovascular response to an appetitive stimulus, which evokes JM conditioning, consists of cardiac accelerations with the BP depressor responses playing a minimal, if any, role. Moreover, these conditioned cardiac increases appear to be due solely to the release of vagal inhibition.     

Heart Rate Changes Accompanying Jaw Movement Pavlovian Conditioning in Rabbits: Concomitant Blood Pressure Adjustments and Effects of Peripheral Autonomic Blockade

Two experiments were conducted to ascertain the cardiovascular accompaniments of differential Pavlovian jaw movement (JM) conditioning. The first examined the blood pressure (BP) changes that accompany the tachycardiac conditioned responses (CRs) associated with JM conditioning. The BP response in all instances consisted of a depressor response that was greater to the reinforced CS+ than CS-, although the magnitude of the CR was quite small. The second experiment determined the effects of peripheral autonomic antagonists on the cardiac accelerations associated with JM conditioning. It was found that the peripheral vagal antagonist methyl scopolamine completely abolished responses to both CS+ and CS-, whereas atenolol, a beta adrenergic antagonist, augmented the response, compared to saline control injections. The JM responses were also affected by the autonomic blockades, with minimal responding occurring in the scopolamine group but slightly more JM CRs in the atenolol group, compared to saline control animals. These results suggest that the major cardiovascular response to an appetitive stimulus, which evokes JM conditioning, consists of cardiac accelerations with the BP depressor responses playing a minimal, if any, role. Moreover, these conditioned cardiac increases appear to be due solely to the release of vagal inhibition.     

Vigilance, active coping, and cardiovascular reactivity during social interaction in young men.

This study of 72 undergraduate men examined the effects of two determinants of cardiovascular response-active coping and vigilance-on blood pressure and heart rate responses to social stressors. Observation of a future debate partner (i.e., vigilance) evoked larger increases in blood pressure than did observation of a less relevant person, apparently through the combination of increases in cardiac output and vascular resistance. Preparation and enactment of efforts to exert social influence (i.e., active coping) evoked heightened blood pressure and heart rate responses through increased cardiac contractility and output. Thus, both vigilance and active coping in social contexts increased cardiovascular reactivity, but apparently through different psychophysiological processes.     

Contrasting effects of social stress and foot-shock on acute cardiovascular response in salt-sensitive rats

Repeated defeat by an aggressive resident attacker rat produces a large decrement in systolic blood pressure (SBP) in male S/JR rats. The present experiments compared the cardiovascular (CV) response of male S/JR rats exposed either to repeated defeat, or to a common laboratory stressor, electric foot-shock. Using the tail-cuff method of determining SBP, the results of Experiment 1 replicated the previous finding that on the second and subsequent exposures, repeated defeat is followed by an acute decrement in SBP (30-40 mm Hg in magnitude). In contrast, repeated exposures to foot-shock were followed by acute increases in SBP (20-40 mm Hg) and in heart rate (HR). In Experiment 2, mean arterial blood pressure (MAP) and HR were measured directly from chronically cannulated male S/JR rats after defeat or exposure to foot-shock: again, defeated males exhibited an acute decrease in MAP, whereas the MAP of rats exposed to foot-shock tended to increase. In Experiment 3 we varied the parameters of shock intensity and the social context of shock exposure. Male S/JR rats exposed to more intense foot-shock than in the previous experiments or to foot-shock while paired with one of the resident attacker rats all exhibited acute increases in SBP. The results of these experiments indicate that CV response to defeat may be qualitatively different from CV response to foot-shock.     

Recovery cycle of the evoked heart rate response in sleeping humans

Paired auditory stimuli, presented during sleep, evoked biphasic heart rate responses of greater than 10-second duration. The magnitude of the response to a second stimulus varies with the time between stimuli. The recovery cycle for human subjects exhibits a subnormal period for both HR peak and trough components at 5-or 6-second interstimulus intervals, and a supernormal period for the HR peak at 9-or 10-second interstimulus intervals. Thus, subnormal and supernormal periods coincide with the peak and trough, respectively, of the biphasic evoked heart rate response.     

The relationship between cardiac reactivity in the laboratory and in real life.

OBJECTIVE: An excessive cardiovascular response to acute stress is a probable risk factor for cardiovascular (CV) disease. Such reactivity is usually assessed from the CV response to laboratory stressors. However, if it is a risk factor, correlated responses must occur in real life. DESIGN: In the present study, we investigated the relationship between the heart rate (HR) response to five laboratory stressors and HR reactivity in the field. MEASURES: HR variation, the response to a real life stressor (public speaking), and the increase in HR with periods of self-reported tense arousal. Ambulatory HR, activity and posture were measured continuously over a 7-hr period. RESULTS: The HR increase to laboratory stressors did not relate to HR variation consistently, but it did relate to the other two field measures. CONCLUSION: The results suggested that a tendency to increased HR reactivity may be a risk factor for cardiovascular disease when combined with exposure to stress.     

Cardiovascular reactivity to and recovery from psychological challenge as predictors of 3-year change in blood pressure.

The authors examined whether cardiovascular reactivity to and recovery from psychological challenge predict 3-year change in blood pressure (BP) among 216 initially normotensive, community-dwelling adults. Clinic BP assessments were conducted at baseline and follow-up. BP and heart rate (HR) readings were obtained before, during, and after 5 psychological tasks at baseline. Following adjustment for traditional predictors of BP and lifestyle factors, poorer systolic BP recovery across the tasks was associated with greater 3-year increases in clinic systolic and diastolic BP. Both diastolic BP recovery and HR recovery were also related to 3-year change in clinic BP, though cardiovascular reactivity measures were not. These findings suggest that the duration of stress-related cardiovascular responses may be important for predicting longitudinal changes in BP.     

Physiological,affective, and behavioral responses to interpersonal conflict among males from families with different levels of cohesion and adaptability

To examine the relation between characteristics of a person's family of origin and cardiovascular, behavioral, cognitive, and affective response to interpersonal conflict, responses of 15 young males from families rated as extreme (EXT) on scales of cohesion (enmeshed or disengaged) or adaptability (chaotic or rigid) were compared to those of 25 young males from families rated as balanced (BAL) on measures of cohesion and adaptability. Subjects participated in two interpersonal role-play conflict situations, one with a male confederate and the other with a female confederate. Measures of heart rate (HR), blood pressure, and indices of both positive and negative verbal and nonverbal behaviors were obtained during each scenario and self-reported measures of positive and negative cognitive self-statements and affective response were obtained following each conflict scene. Results showed that, in contrast to BAL males, EXT males exhibited more negative verbal and nonverbal behavior, less positive nonverbal behavior, higher ratings of state anxiousness during conflict, and higher HR responses during the interaction with the male confederate than the female confederate. These findings suggest that exposure to a family environment with extreme levels of cohesion and adaptability impacts how an individual responds to interpersonal conflict in young adulthood.     

Neuropeptide and cardiovascular responses to intravenous catheterization in normotensive and hypertensive blacks and whites

Research suggests that heightened cardiovascular and neuroendocrine (typically catecholamine) responses to stressors may lead to the development of hypertension and that there may be race differences in patterns of reactivity that are potentially pathogenic. Certain neuropeptides exert profound effects on blood pressure (BP) and heart rate (HR), yet no published studies have examined relationships between these peptides, hypertensive status, race, and reactivity. Seventeen Black and 20 White normotensive and borderline-hypertensive male 19- to 50-year-olds underwent intravenous catheterization while cardiovascular and neuropeptide responses to the stress of being catheterized were examined. Results indicate that, in response to the stressor, Black hypertensives, showed significantly lower endorphin levels compared to Black normotensives, and White hypertensives showed significantly higher levels of beta-endorphin compared to White normotensives. Groups were not significantly different in endorphin levels at recovery. Black hypertensives also showed significantly higher stressor-induced HR and systolic and diastolic BP compared to White hypertensives and normotensives. Lower levels of beta-endorphin and lower urine sodium excretion were associated with higher BP and HR.     

From acquisition to consolidation: on the role of brain-derived neurotrophic factor signaling in hippocampal-dependent learning

One of the most rigorously investigated problems in modern neuroscience is to decipher the mechanisms by which experience-induced changes in the central nervous system are translated into behavioral acquisition, consolidation, retention, and subsequent recall of information. Brain-derived neurotrophic factor (BDNF) has recently emerged as one of the most potent molecular mediators of not only central synaptic plasticity, but also behavioral interactions between an organism and its environment. Recent experimental evidence indicates that BDNF modulates synaptic transmission and plasticity by acting across different spatial and temporal domains. BDNF signaling evokes both short- and long-term periods of enhanced synaptic physiology in both pre- and postsynaptic compartments of central synapses. Specifically, BDNF/TrkB signaling converges on the MAP kinase pathway to enhance excitatory synaptic transmission in vivo, as well as hippocampal-dependent learning in behaving animals. Emerging concepts of the intracellular signaling cascades involved in synaptic plasticity induced through environmental interactions resulting in behavioral learning further support the contention that BDNF/TrkB signaling plays a fundamental role in mediating enduring changes in central synaptic structure and function. Here we review recent literature showing the involvement of BDNF/TrkB signaling in hippocampal-dependent learning paradigms, as well as in the types of cellular plasticity proposed to underlie learning and memory.     

Heart rate responses to induced challenge situations in greylag geese (Anser anser)

Adequate short-term responses to stressors are of great importance for the health and well-being of individuals and factors modulating the physiological stress response (e.g., controllability, suddenness, familiarity) of a stimulus are well described under laboratory conditions. In the present study we aimed at investigating the stress response in greylag geese (Anser anser) in the field, confronting individuals with naturally occurring stressors. We measured beat-to-beat heart rate (HR) via fully implanted transmitters during three different experimental challenges: (1) catching and holding, (2) confrontation with a model predator, and (3) approach by different humans. We compared this to a control period and HR during agonistic encounters, a naturally occurring stressor. All three experimental situations evoked a HR increase. Highest HR responses were elicited by catching and holding the animals. In the third experiment, HR responses were greatest when the geese were approached by a human stranger (i.e., somebody the geese have never seen before). Hence, geese discriminated between different kinds of stressors and adjusted their physiological response depending on the type of stressor. Our results show that geese were able to discriminate between individual humans. In line with a number of lab studies, we suggest that particularly the controllability of certain situation determines the intensity of the HR response, also in a natural setting in the field.     

Neonatal auditory habituation and state change

Groups of newborn babies were exposed to various series of 90 dB SPL noiseband stimuli or to simulated (control) stimuli, while their heart rates (HR) and states of behavioural arousal were monitored. In general the response to stimulation was an accelerative HR change which tended to decrease with repeated stimulation. This seemed to provide evidence of habituation to the auditory stimuli. However, the HR response to sound depended on prestimulus HR and on state, and, when these effects were removed by regression techniques, the progressive decrease in evoked HR with repeated stimulation disappeared, apart from the first few trials. This implied that there was HR habituation to the initial stimuli, but not subsequently, when the apparent HR “habituation” reflected progressive endogenous state changes.     

Neuromuscular blocking drugs and heart rate changes after direct nerve stimulation and during classical conditioning in cats.

Two experiments investigated cardiovascular responses to several common neuromuscular blocking compounds. Experiment 1, employing 16 cats, assessed ganglionic transmission in sympathetic and parasympathetic systems controlling heart rate and blood pressure after d-tubocurarine chloride (d-T.C.), dimethyl d-tubocurarine iodide (D. d-T.I.), succinylcholine chloride (SC), or saline. Cardiovascular responses to sympathetic stimulation were essentially unaffected at drug levels that blocked evoked electromyograms; however, vagally evoked bradycardia and corresponding blood pressure decrease were blocked by d-T.C. and redduced by D. d-T.I. and SC. Experiment 2 compared heart responses of 12 cats under the same blocking compounds during differential classical aversive conditioning. Differential conditioned responses and unconditioned responses occurred under D. d-T.I., less under SC, but not under d-T.C. However, animals trained under d-T.C. and tested under D. D-T.I. showed differential conditioned responses.     

Cardiac and neuroendocrine responses to exposure therapy in height phobics: desynchrony within the 'physiological response system'

Subjective, behavioral, cardiovascular and neuroendocrine responses were intensively monitored in two height phobics over a full course of exposure therapy and at follow-up. Both subjects showed rising cortisol responses and stable, non-extinguishing norepinephrine responses to height exposure over the course of treatment, while improvement occurred in subjective and behavioral response systems. They had differing heart rate responses. Despite desynchrony amongst anxiety response systems and within the physiological 'system' at treatment conclusion, both subjects had successful outcomes which were preserved at follow-up. Implications for the measurement of the 'physiological response system' in behavioral research are discussed.