Bradford N. Bunnell

Comparison of stress response in male and female rats: pituitary cyclic AMP and plasma prolactin, growth hormone and corticosterone.

Three potent stressors (forced running, immobilization, and footshock) were found to increase levels of cyclic AMP in the pituitaries of both female and male rats. The pituitary cyclic AMP response in females was generally similar to that observed in males. The tested stressors elevated both plasma corticosterone and prolactin and decreased plasma growth hormone. Plasma corticosterone rose more rapidly in females than in males following stress. Control growth hormone levels were higher in male rats. There was no clear cause and effect relationship between elevations of pituitary cyclic AMP and changes in plasma levels of prolactin, corticosterone, and growth hormone.

Effects of repeated stress on pituitary cyclic AMP, and plasma prolactin, corticosterone and growth hormone in male rats

The effects of five putative stressors (saline injection, cold exposure, forced running, immobilization, and footshock) on levels of pituitary cyclic AMP, plasma prolactin, corticosterone and growth hormone were examined. In naive rats exposed to 15 min of these stressors for the first time, running, immobilization and footshock increased levels of pituitary cyclic AMP, plasma corticosterone and prolactin and decreased growth hormone, typical of stress response in the rat. Cold exposure only increased corticosterone and saline injection did not affect any measured parameter. In rats chronically exposed to the same stressor (once a day for 15 min) for 10 days immediately prior to the experiment, an attenuated pituitary cyclic AMP and plasma prolactin response was seen upon application of 15 min of that stressor on the day of the experiment, compared to the responses observed in the naive rats.

Activity wheel running reduces escape latency and alters brain monoamine levels after footshock

We examined the effects of chronic activity wheel running on brain monoamines and latency to escape foot shock after prior exposure to uncontrollable, inescapable foot shock. Individually housed young (approximately 50 day) female Sprague-Dawley rats were randomly assigned to standard cages (sedentary) or cages with activity wheels. After 9-12 weeks, animals were matched in pairs on body mass. Activity wheel animals were also matched on running distance. An animal from each matched pair was randomly assigned to controllable or uncontrollable inescapable foot shock followed the next day by a foot shock escape test in a shuttle box. Brain concentrations of norepinephrine (NE), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), 5-hydroxytryptamine (5-HT), and 5-hydroxyindole acetic acid (5-HIAA) were assayed in the locus coeruleus (LC), dorsal raphe (DR), central amygdala (AC), hippocampus (CA1), arcuate nucleus, paraventricular nucleus (PVN), and midbrain central gray. After prior exposure to uncontrollable foot shock, escape latency was reduced by 34% for wheel runners compared with sedentary controls. The shortened escape latency for wheel runners was associated with 61% higher NE concentrations in LC and 44% higher NE concentrations in DR compared with sedentary controls. Sedentary controls, compared with wheel runners, had 31% higher 5-HIAA concentrations in CA1 and 30% higher 5-HIAA concentrations in AC after uncontrollable foot shock and had 28% higher 5-HT and 33% higher 5-HIAA concentrations in AC averaged across both foot shock conditions. There were no group differences in monoamines in the central gray or in plasma prolactin or ACTH concentrations, despite 52% higher DA concentrations in the arcuate nucleus after uncontrollable foot shock and 50% higher DOPAC/DA and 17% higher 5-HIAA/5-HT concentrations in the PVN averaged across both foot shock conditions for sedentary compared with activity wheel animals. The present results extend understanding of the escape-deficit by indicating an attenuating role for circadian physical activity. The altered monoamine levels suggest brain regions for more direct probes of neural activity after wheel running and foot shock.

Treadmill exercise training augments brain norepinephrine response to familiar and novel stress

In a test of hypothalamic-pituitary-adrenal (HPA) cortical and hypothalamic-pituitary-gonadal (HPG) interaction during familiar and novel stress, we previously reported that treadmill exercise training led to blunted plasma adrenocorticotrophin (ACTH) response to acute treadmill running but a hyper-responsiveness of ACTH after novel immobilization. In this follow-up analysis, we examined whether those results might be plausibly explained by a similar effect of treadmill exercise training on increased levels of norepinephrine (NE) in hypothalamic and limbic brain regions which synergize to modulate the release of ACTH during stress. Ovariectomized Sprague-Dawley rats that had been exercise trained by treadmill running or remained sedentary for 6 weeks received intramuscular injections of estradiol benzoate (Eb) or sesame oil on each of 3 days prior to 15 min of familiar treadmill running or novel immobilization. Treadmill exercise training, regardless of Eb treatment or type of stress, increased NE levels in the paraventricular (PVN), arcuate, medial preoptic, and ventromedial areas of the hypothalamus and protected against depletion of NE in the locus coeruleus, amygdala, and hippocampus. We conclude that treadmill exercise training has a hyperadrenergic effect in brain areas that modulate hypothalamic regulation of ACTH release during stress that is independent of HPA-HPG interaction and novelty of the stressor. To help elucidate these findings, the effects of treadmill exercise training on A1-A2 nuclei which innervate the PVN and their relationship with the limbic and hypothalamic responses we report require study.

Septal ablation and the social behavior of the golden hamster

Abstract In four experiments, the effect of septal ablation on the social behavior of the hamster was observed. The results indicated that septal ablation increased the aggressiveness of both socially naive and experienced dominant hamsters. If, however, the septal hamster experienced defeat by an opponent during preoperative testing, no postoperative increment in aggression was observed. All septal hamsters, whether aggressive or not, either ceased to display hoarding behavior or hoarded very little. All septal hamsters also showed persistent approach responses to their opponents. Paired contests between septal animals resulted in high levels of aggression with one septal in each pair being defeated and assuming a submissive status.

Amygdaloid lesions and social behavior in the golden hamster.

Abstract Changes in the amount and kind of social behavior were observed in male hamsters following amygdalectomy. In comparison to normals and operated controls, subjects with bilateral lesions of the amygdala showed a reduction in the total amount of social interaction with conspecifics. Frequency of aggressive behaviors was reduced in most preoperatively aggressive animals while submissive behavior was reduced in preoperatively submissive subjects. There was no change in the sequencing of behavioral acts and both preoperatively dominant and submissive animals retained their social status after surgery.

Activity Wheel Running Blunts Increased Plasma Adrenocorticotrophin (ACTH) after Footshock and Cage-Switch Stress

We examined whether chronic circadian physical activity attenuates hypothalamic-pituitary-adrenal hormone responses after footshock with or without cage-switch stress. Young (45 g) male Fischer 344 rats were randomly assigned to individual suspended home cages (HC) or cages with activity wheels (AW) (12 h:12 h light-dark photoperiod). After 6 weeks, each animal from a pair matched on mass (HC and AW) and average weekly running distance (AW) was randomly assigned to controllable or uncontrollable footshock on 2 days separated by 24 h. Half the animals were returned to the HC after the first day of shock, and half were switched to a new shoebox cage. One animal of each pair could end the shock for both rats by performing an FR-2 lever press. The yoked animal could not control the shock. After shock on Day 2, trunk blood was collected after decapitation. Plasma adrenocorticotrophin (ACTH), corticosterone, and prolactin were determined by radioimmunoassay. ANOVA for a 2 Group (AW vs. sedentary) x 2 Test (controllable vs. uncontrollable shock) x 2 Condition (HC vs. cage-switch) design indicated a Group x Test x Condition effect [F(1, 48) = 5.07, p = 0.03] and a Test main effect [F(1, 47) = 6.93, p = 0.01] for ACTH. ACTH was higher for sedentary animals after uncontrollable footshock under cage-switch conditions and higher after uncontrollable versus controllable footshock when averaged across groups and cage conditions. No effects were found for corticosterone or prolactin. Our results extend to activity wheel running prior findings of a cross-stressor attenuation in plasma [ACTH] in response to cage-switch after treadmill exercise training, though the cross-stressor effect was additive with footshock. Consistent with our prior reports, the cross-stressor effect of wheel running was not apparent after footshock administered under home-cage conditions.

Hyperresponsiveness of the rat neuroendocrine system due to repeated exposure to stress

Sequential exposure to stressors may elicit a period of endocrine hyperresponsiveness during which plasma hormone concentrations reach higher levels after repeated exposure to a stressor compared to levels after initial exposure. The present study was designed to further characterize hyperresponsiveness to repeated stress and determine if hyperresponsiveness is dependent upon repeated exposure to the same stressful stimuli. In Experiment 1, rats were stressed by inescapable tailshock, immobilization or exposure to shock chamber without shock for one, two, three, four or five consecutive days (15 min/day). In rats exposed to tailshock, corticosterone (CS) levels in plasma collected on days 2, 3, 4 and 5 were higher than CS levels following acute tailshock on day 1, demonstrating hyperresponsiveness to repeated tailshock. Hyperresponsiveness of CS secretion also occurred in groups of rats restrained for four or five days. No changes occurred in the CS response of animals repeatedly exposed to immobilization. Prolactin (PRL) levels were not affected by repeated exposure to the stressors. However, PRL values were different between the stress conditions and indicated that the order of stressor severity was tailshock greater than immobilization greater than exposure to shock chamber without shock. In Experiment 2, rats were exposed to either one or two consecutive days of tailshock or immobilization. Other rats were exposed to either tailshock or immobilization on the first day, then switched to the other stressor on the next day. Hyperresponsiveness to repeated tailshock, but not immobilization, was reflected in plasma levels of CS and adrenocorticotropic hormone (ACTH), but not PRL. Hyperresponsiveness of CS and ACTH secretion also was found in rats first stressed by immobilization then switched to tailshock, demonstrating that hyperresponsiveness is not dependent upon reexposure to familiar stressful stimuli. However, hyperresponsiveness did not occur in rats first exposed to tailshock then switched to immobilization. The data suggest that both immobilization and tailshock primed the organism to hyperrespond, but only the more severe stressor (tailshock) elicited hyperresponsiveness of the neuroendocrine system.

Treadmill exercise training and estradiol differentially modulate hypothalamic-pituitary-adrenal cortical responses to acute running and immobilization

It is generally believed that physical fitness promotes health by attenuating responsiveness to other stressors. The experimental evidence for this belief is limited and does not extend to interactions between the hypothalamic-pituitary-adrenal cortical (HPA) and hypothalamic-pituitary-gonadal (HPG) axes. We tested the hypothesis that treadmill exercise training would lead to an estrogen-dependent hyporesponsiveness of the HPA axis that would generalize to immobilization stress. Ovariectomized female Sprague-Dawley rats (N = 74) that had been treadmill trained (TT) or sedentary for 6 weeks received intramuscular injections of estradiol benzoate (Eb) or sesame oil on each of 3 days prior to 15 min of acute treadmill running or immobilization. Plasma (adrenocorticotrophin) (ACTH), (corticosterone) (B) and (prolactin) (PRL) were determined from trunk blood by radioimmunoassay and compared in a 2 group (TT vs. sedentary)-by-2 treatment (Eb vs. oil)-by-2 acute stressor (running vs. immobilization) design. Home-cage (HC) animals (N = 24) provided baseline hormone levels. ACTH and B levels were elevated after stressors in animals treated with either Eb or oil compared to HC, but increases in PRL after stressors were dependent on Eb. Treadmill exercise training led to an attenuation of ACTH and prolactin to running, but the attenuation did not generalize to immobilization. In contrast, treadmill exercise training led to a hyperresponsiveness of ACTH. Treadmill training did not modulate prolactin responses to immobilization. The modulating effects of the estradiol treatment are consistent with an interaction of the HPA and HPG axes in response to stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Performance correlates of social behavior and organization: Social rank and omission of reinforcement in rhesus monkeys (M. mulatta)

The performance of 22 adult male rhesus monkeys on a Fixed Interval 1-min reinforcement schedule was examined under conditions where the reinforcement probabilities were either 1.00 or .80. The results were then related to the social rank of animals at the time that they were taken from their social groups. Both high and low ranked animals reached criterion performance in the same number of trials. In general, high ranking animals responded at lower rates than low ranking animals when the reinforcement probability was 1.00. When the reinforcement probability was shifted to .80, all animals showed an increase in responding after nonreinforced intervals as compared with responses after reinforced intervals. The higher ranked animals tended to have a higher ratio of nonreinforced to reinforced responses than lower ranked animals.