The Effects of Conflict on Tonic Levels of Blood Pressure in the Genetically Borderline Hypertensive Rat

Studies of aversive conditioning in animals have seldom elicited tonic elevations in blood pressure (BP) equivalent to those which produce pathological changes in humans. While it is possible that psychological factors are not that important in the etiology of hypertension, it is also possible that the failure to elicit large tonic elevations in BP in animals may be due either to stressors which are insufficiently potent and/or to an inadequate physiological model. The present study sought to maximize the probability of producing large tonic changes in BPs by using a conflict paradignt in a genetic strain of rats which develops systolic BPs in the borderline hypertensive area (c. 150 mmHg). Forty-eight male F₁ generation offspring of spontaneously hypertensive rats mated with normotensive controls were randomly split into three groups: experimental (subjected to 3 weeks of avoidance training and 12 weeks of conflict in conditioning cages), mild restraint control (placed in conditioning cages daily but not shocked), and maturation control (neither shocked nor restrained) groups. Animals subjected to conflict gradually developed tonic levels of systolic BP well into the hypertensive range (c. 185 mmHg). Restraint control animals also showed some elevation (c. 165 mmHg), but maturational controls showed no change (c. 150 mmHg). The saliency of this animal model for the study of stress-induced hypertension is discussed.     

Blood pressure and cardiac changes during signalled and unsignalled avoidance in dogs

Alterations in blood pressure (BP) during two aversive behavioral tasks were studied in five chronically-prepared dogs. During a signalled-avoidance task, BP levels were not altered, although heart rate (HR) increased. While propranolol (0.3 mg/kg, IA) led to slight increases in resting pressure, and phenoxybenzamine (1.0 mg/kg) reductions, the tachycardia at avoidance onset was not affected. Exposure to an unsignalled-avoidance task led to elevated diastolic BP levels during a preavoidance period and to increases in systolic BP, HR and aortic dP/dt at the inception of the avoidance session. Again, neither drug affected the tachycardia during avoidance, but both agents precluded BP and aortic dP/dt increases. Patterns of intercorrelations among cardiovascular variables were similar for both tasks, and suggested that the basis of the BP maintenance shifted from vasomotor to cardiac control during the avoidance periods. The differential cardiovascular adjustments during these tasks could not be accounted for in terms of differences in response rate. Rather, the critical variable seemed to be the amount of feedback the animal received for responding.     

Graded acquisition of an instrumental avoidance response by the spinal rat.

Eight pairs of spinal rats were exposed to an instrumental conditioning paradigm in which one animal served as the experimental and the other as a yoked control animal. An electrode, inserted into the experimental animal's foot, contacted an aqueous solution delivering shock to both animals. Leg flexion terminated the shock. Following two consecutive min without shock, the experimental animal's solution was raised an additional millimeter and training was re-instated. This procedure was repeated 4 times, or until the experimental animal failed to reach the 2 min criterion. In Run 1, one leg was trained; during Run 2, the contralateral leg was used. In addition, the animal which served as the experimental in Run 1 served as the yoked control in Run 2 and vice versa. The results indicate that the spinal rat is capable of acquiring successively higher criteria in an instrumental conditioning routine. In conjunction with previous results, these findings suggest that instrumental avoidance learning can occur in the spinal cord.     

Myocardial Degeneration and Cardiac Arrest in Squirrel Monkey: Physiological and Psychological Correlates

Behavioral factors and cardiovascular changes associated with myocardial degeneration and cardiac arrest induced by shock avoidance stress were studied. Pairs of avoidance and yoked squirrel monkeys were exposed to a 24-hr session. Myocardial degeneration and cardiac arrest were more readily induced in avoidance than yoked monkeys. The cardiac lesions were not related to body weight, aggressive behavior, or number of shocks received during stress, but an increased heart rate without hypertension during the first stress hour was more evident in avoidance than yoked monkeys. These cardiac changes were attributed to an autonomic disturbance associated with the response contingencies of the avoidance situation. An autonomic effect also appeared to be involved with stress-induced death. These deaths were characterized by a sudden, severe bradycardia without initial hypotension and cardiac arrest which was attributed to either parasympathetic activation or sympathetic inhibition. While heart rate decreased in all monkeys, stress-induced death followed only in monkeys which gave up and stopped contending with the stress. Thus, stress-induced myocardial changes and death were related to autonomic disturbances precipitated by psychological stress.     

Hemodynamic and metabolic adjustments during exercise and shock avoidance in dogs.

The purpose of this study was to examine whether the hemodynamic and metabolic consequences of a physical (treadmill excercise) and behavioral (signaled shock-avoidance) stressor could be differentiated. To do this, direct continuous recordings of cardiac output, systolic and diastolic blood pressure, and discrete determinations of the arterial-mixed venous oxygen ((a-v)O2) content difference were analyzed in six dogs during exposure to three grades of treadmill exercise and when working on a shock-avoidance task. The results indicated that in five animals the relationship between cardiac output and the (a-v)O2 difference during shock-avoidance conditioning was significantly different from the corresponding pattern observed during exercise. In four animals the data suggested that avoidance conditioning, relative to exercise stress, elicited overperfusion. Behavioral stress also produced reliable elevations in diastolic and systolic blood pressure. These results suggest that, when compared to physical stress, behavioral stress can produce a dissociation of cardiovascular and metabolic processes in the presence of acute pressor responses.     

Cardiovascular changes prior to exercise in appetitive and avoidance conditioning in rats

Blood pressure and heart rate changes were monitored in rats immediately before exercise--running up a set of stairs 54 cm long. The rats were divided into two groups: (1) avoidance, (2) food intake. For both groups the run was preceded by an 80 dB buzzer lasting 5-15 sec. When the criterion for the conditioned response to the buzzer was achieved all avoidance rats showed significant increases of heart rate, systolic and diastolic blood pressure before exercise, during the buzzer. Of the food intake group all but one showed no significant cardiovascular changes before exercise, in response to the sound. It is concluded that exercise itself in these experiments could not have contributed significantly to the anticipatory cardiovascular changes, unless it is associated with an aversive event.     

Instrumental avoidance conditioning of increased leg lowering in the spinal rat

Five pairs of chronic spinal rats were trained to lower a hind leg and then were tested for retention using a counter-balanced instrumental avoidance paradigm in which one animal served as the experimental and the other as a yoked control subject. An additional three pairs of rats were used in this paradigm after their lumbosacral spinal cords had been removed by aspiration. The results indicate that the chronic spinal rat is capable of instrumental avoidance conditioning when leg lowering is the response, and that the lumbosacral spinal cord is essential for this phenomenon.     

Discriminated lever press avoidance conditioning in male and female rats

Discriminated lever press avoidance and step through passive avoidance conditioning were studied in male and female rats. In lever press avoidance female rats showed superior avoidance performance, less intertrial responding and shorter durations of leverholding than male rats. Castration of males tended to improve their avoidance performance, whereas ovariectomy had no effect. In passive avoidance more males than females showed an avoidance response. From these results it is concluded that aversive stimulation seems to elicit different behavior tendencies in male and female rats rendering males less prepared for active avoidance, but at the same time more prepared for passive avoidance conditioning. The data do not support the hypothesis that sex differences in activity underly the dimorphism in active and passive avoidance conditioning.     

Controllable versus uncontrollable stressors bi-directionally modulate conditioned but not innate fear

Fear conditioning and fear extinction play key roles in the development and treatment of anxiety-related disorders, yet there is little information concerning experiential variables that modulate these processes. Here we examined the impact of exposure to a stressor in a different environment on subsequent fear conditioning and extinction, and whether the degree of behavioral control that the subject has over the stressor is of importance. Rats received a session of either escapable (controllable) tail shock (ES), yoked inescapable (uncontrollable) tail shock (IS), or control treatment (home cage, HC) 7 days before fear conditioning in which a tone and foot shock were paired. Conditioning was measured 24 h later. In a second experiment rats received ES, IS or HC 24 h after contextual fear conditioning. Extinction then occurred every day beginning 7 days later until a criterion was reached. Spontaneous recovery of fear was assessed 14 days after extinction. IS potentiated fear conditioning when given before fear conditioning, and potentiated fear responding during extinction when given after conditioning. Importantly, ES potently interfered with later fear conditioning, decreased fear responding during fear extinction, and prevented spontaneous recovery of fear. Additionally, we examined if the activation of the ventral medial prefrontal cortex (mPFCv) by ES is critical for the protective effects of ES on later fear conditioning. Inactivation of the mPFCv with muscimol at the time of the initial experience with control prevented ES-induced reductions in later contextual and auditory fear conditioning. Finally, we explored if the protective effects of ES extended to an unconditioned fear stimulus, ferret odor. Unlike conditioned fear, prior ES increased the fear response to ferret odor to the same degree as did IS.     

Avoidance conditioning in mice as a function of their mothers' training

Prior to mating, inbred female mice were exposed to 1 of 4 conditions for 15 days: 50 trials of avoidance conditioning per day; equivalent (yoked) exposure to conditioned stimulus (CS) and shock, but without the response contingency; yoked exposure to the CS alone; or no experimental treatment. Within 48 hr after birth the offspring of these females were transferred to unrelated foster mothers. The treated females served as foster mothers for the offspring of untreated females. When the adult avoidance conditioning performance of the offspring was analyzed, an interaction was found between the sex of the offspring, the treatment of the mothers, and the developmental period during which the maternal treatment influenced the offspring. In general, the prenatal effect of maternal treatment was the reverse of the postnatal effect, and its effect, while somewhat greater on female offspring, also was the reverse of its effect on male offspring.     

The impact of physical proximity and attachment working models on cardiovascular reactivity: Comparing mental activation and romantic partner presence

Close relationships, especially high‐quality romantic relationships, are consistently associated with positive physical health outcomes. Attenuated cardiovascular reactivity is one physiological mechanism implicated in explaining these effects. Drawing on attachment and social baseline theories, this experimental study evaluated two potential affiliative cues as mechanisms through which romantic relationships may attenuate cardiovascular reactivity to a laboratory‐based stressor. Prior to a cold pressor task, 102 participants were randomly assigned to either have their partner physically present, call upon a mental representation of their partner, or think about their day during the stressor. Consistent with our preregistered hypotheses, participants in both the partner present and mental activation conditions had significantly lower blood pressure (BP) reactivity during the cold pressor task compared to control participants for both systolic (d = ?0.54) and diastolic BP (d = ?0.53), but no significant differences emerged for heart rate or heart rate variability. Although participants in the partner present and mental activation conditions had similar BP reactivity to the cold pressor task, those in the partner present condition reported significantly less pain as a result of the task. The difference in BP reactivity by condition was moderated—BP reactivity was greater for people with lower self‐reported relationship satisfaction. The results suggest that accessing the mental representation of a romantic partner and a partner’s presence each buffer against exaggerated acute stress responses to a similar degree.     

Behavioral control, aversive stimulus frequency, and pituitary-adrenal response

Six females rats were trained to lever press under a free operant shock-postponement schedule. Each subject had a yoked control which received shock whenever the subject did. The shock-postponement interval (R-S) was varied from 5, 10, 20, 40, to 80 s over blocks of sessions. Corticosteroid levels were taken prior to training and before and after selected sessions. The rate of responding and the rate of shock were inversely related to the R-S interval. Corticosteroid levels were unrelated to the R-S parameter, although steroid samples taken during experimental periods were significantly elevated above preexperimental basal levels. Corticosteroid levels of avoidance subjects were significantly higher than basal levels at the beginning of a session. By the end of a session, these levels were significantly reduced, although still above basal levels. The results were reversed for the yoked control subjects. Their presession corticosteroid levels, although elevated over basal levels, were lower than postsession levels. The implication of these results for the notion that anticipation and control affect levels of arousal is discussed.     

Expectancy of the UCS during Avoidance Conditioning of the SCR

Two studies are reported which investigated the relationship between expectancy of the UCS (shock) and avoidance conditioning of the skin conductance response (SCR). Subjects were allowed to avoid the shock UCS if they gave criterion magnitude SCRs to a warning tone preceding the shock. Expectancy of the UCS was monitored on a trial-by-trial basis during the avoidance conditioning process. It was found in Experiment I that SCR conditioning occurred only among subjects who had accurate expectancies of shock omission relative to their yoked controls. However, those subjects who were able to accurately predict shock omission were not able to verbalize the response-reinforcement contingency during a postconditioning questionnaire. Experiment II revealed that only subjects with accurate expectancies concerning the shock behaved differently from their yoked controls when given informative instructions about the response-reinforcement contingency. These data indicate that individual differences in the accuracy of UCS expectancy are positively related to SCR avoidance conditioning. This relationship has gone undetected in previous research because of the exclusive reliance upon verbal postconditioning questionnaires.     

Contribution of the amygdala to learning and performance of conditional fear.

The amygdaloid complex appears to be an essential component in the neural systems mediating some forms of aversive Pavlovian conditioning. The relative contribution of this structure to acquisition and performance during fear conditioning was assessed by making temporary lesions in the amygdala prior to training or retention testing in a single-trial Pavlovian conditioning preparation. Microinjection of lidocaine HCl (5.0%, 1.0 microliters) into the amygdala prior to the presentation of a CS signalling footshock resulted in a significant attenuation of the performance of conditional fear, as indexed by the amount of time rats spent engaged in defensive freezing behavior during the retention session. However, similar treatment with lidocaine prior to the training session, during which the CS and UCS were paired, resulted in only a weak reduction in subsequent responding. Thus, while both acquisition- and performance-related processes take place within the amygdala, it appears that the latter are more sensitive to disruption using the present procedures. These results are discussed in terms of the general role played by this structure in aversive learning and motivational processes.     

Glutamatergic activation of anterior cingulate cortex produces an aversive teaching signal

Noxious stimuli have motivational power and can support associative learning, but the neural circuitry mediating such avoidance learning is poorly understood. The anterior cingulate cortex (ACC) is implicated in the affective response to noxious stimuli and the motivational properties of conditioned stimuli that predict noxious stimulation. Using conditioned place aversion (CPA) in rats, we found that excitatory amino acid microinjection into the ACC during conditioning produces avoidance learning in the absence of a peripheral noxious stimulus. Furthermore, microinjection of an excitatory amino acid antagonist into the ACC during conditioning blocked learning elicited by a noxious stimulus. ACC lesions made after conditioning did not impair expression of CPA. Thus, ACC neuronal activity is necessary and sufficient for noxious stimuli to produce an aversive teaching signal. Our results support the idea that a shared ACC pathway mediates both pain-induced negative affect and a nociceptor-driven aversive teaching signal.     

Effect of paradoxical sleep deprivation and stress on passive avoidance behavior

Previous studies have shown that several types of stress can induce memory impairment. However, the memory effects of paradoxical sleep deprivation (PSD), a stressor in itself, are unclear. We therefore compared passive avoidance behavior of rats undergoing PSD and PSD stress yoked-control (PSC) using the "reversed flowerpot method." When rats were kept isolated on a PSC platform for 24 h immediately after criterion training, retention trials showed impaired aversive memory storage. When delayed for 24 h after criterion training, PSC stress did not disrupt retention performance. In rats subjected to PSD, either immediately or 24 h after criterion training, there was no disruption of aversive memory consolidation. These results suggest that, during stress, paradoxical sleep plays a role in erasing aversive memory traces, in line with the theory that we "dream in order to forget."     

Hemodynamic Reactivity to Laboratory Stressors in Healthy Subjects: Influence of Gender and Family History of Cardiovascular Diseases

Although laboratory stressor tests have been applied as a preliminary protocol in some cardiovascular studies, there is a lack of data comparing the pressor and chronotropic responses among the main stressor tests. Therefore, the aim of this study was to evaluate the variability in hemodynamic responsiveness to the main stressor tests, establish a hyperresponsiveness cutoff criterion and analyze the influence of gender and family history of cardiovascular diseases (CVDs) in healthy subjects. We examined hemodynamic responses to physical (cold pressor and handgrip tests) and mental (Stroop color-word test) stressors in 98 subjects (48 males and 50 females) without CVDs. All stressor tests resulted in increased blood pressure (BP) levels, which were lower and less dispersed in the handgrip test compared to the cold pressor test. Adopting the 75^th percentile as the cutoff in our data, we classified subjects exhibiting absolute pressor changes equal to or higher than 14, 24 and 36 mmHg in systolic and 9, 13 and 24 mmHg in diastolic BP during the handgrip, Stroop and cold pressor test, respectively, as hyperresponsives. Males exhibited greater (p<0.05) increases in systolic BP in the handgrip (11% vs. 8%) and cold pressor (25% vs. 21%) tests and in diastolic BP in the handgrip (12% vs. 7%) and Stroop (22% vs. 19%) tests than females. A positive association between family history of CVDs and pressor hyperreactivity to stressor tests was observed. We propose using the 75^th percentile of hemodynamic sample values as a cutoff criterion to classify individuals as pressor or chronotropic hyperreactives. We conclude that hemodynamic responsiveness to stressor tests in healthy subjects is positively influenced by male gender and family history of CVDs.     

Posttraining intracranial self-stimulation ameliorates the detrimental effects of parafascicular thalamic lesions on active avoidance in young and aged rats

To evaluate whether intracranial self-stimulation (SS) ameliorates conditioning deficits induced by parafascicular nucleus (PF) damage in young and aged rats, the authors gave rats a daily session of 2-way active avoidance until a fixed criterion was achieved. Four experimental groups were established in both young and aged rats: SS treatment after every conditioning session (SS groups), pretraining PF lesions (lesion groups), PF lesions and SS treatment (L + SS groups), and controls. SS treatment not only canceled the detrimental effects of PF lesions, but also improved conditioning in lesioned rats (L + SS groups). This effect was more powerful in aged rats. SS treatment compensated for memory deficits generated by hypofunctionality of arousal systems such as that involving the PF.     

Physiologic responses to cognitive challenge during pregnancy: effects of task and repeat testing.

Physiological responses to stress during pregnancy are believed to influence birth outcomes. Researchers have studied pregnant women in laboratory stressor paradigms to investigate these associations, yet normative data on cardiovascular and respiratory responses to laboratory challenge during pregnancy are not yet established. To begin to establish such normative data, this study examined the effects of task and repeat stressor exposure on reactivity in third-trimester pregnant women. Thirty-one healthy pregnant women (mean age=27 years; range 18-36) between the 33rd and 39th week of pregnancy, were instrumented for continuous electrocardiography, blood pressure (BP), and respiration data. Subjects rested quietly for a 5-min baseline and then performed both a mental arithmetic stressor and a Stroop color-word-matching task, each 5 min in length and each followed by a 5-min recovery period. The order of the tasks was counterbalanced. After each 5-min period, subjects rated the period on a 10-point stress scale. Averaged across task type and challenge period, systolic and diastolic BP and respiration rate increased significantly in response to cognitive challenge, but heart rate (HR) did not. When data were examined for task and period effects, the following results emerged: the Stroop task elicited significantly greater systolic BP and HR reactivity than the arithmetic task, yet subjects rated the arithmetic task as more stressful. Averaged across task type, subjects showed greater systolic BP reactivity during the second challenge period compared to the first. Finally, women's BP tended to drift upward and did not return to baseline during the first recovery period. These findings indicate that averaging data across tasks and periods can obscure the time course of response patterns that may be important in the study of associations between maternal stress and perinatal development, as well as in other research on reactivity to repeat stress exposure.     

Correlations between paradoxical sleep and shuttle-box conditioning in rats

Eighteen male Wistar rats were given one daily two-way active avoidance conditioning session followed immediately by 5 hr of sleep recording, for 5 consecutive days. The group of rats that achieved 80% or greater avoidance in some of the 5 training sessions showed significant linear increases of paradoxical sleep (PS), compared with baseline levels, throughout the successive conditioning sessions. Furthermore, (a) the group of rats showing PS increases (more than 1 SD above baseline) after some of the training sessions achieved a significantly higher final number of avoidances than the remaining animals: (b) a high and positive correlation was observed between avoidance increases in the 3rd conditioning session and previous PS; and (c) maximum increases in correct performance often occurred following high PS increases. It is concluded that PS increases facilitate the consolidation of learning.