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Biomedical subjects

A Armario

Publications and source records attributed to A Armario.

At least 73 records · Page 4Linked to original sources

Role of glucocorticoids and catecholamines on hepatic thiobarbituric acid reactants in basal and stress conditions in the rat.

Thiobarbituric acid-reactants (TBARs) are considered to be an index of lipid peroxidation. In the present experiments, the effect of stress and hormones on hepatic TBARs levels was studied in Sprague-Dawley rats. In unstressed conditions adrenalectomized rats showed higher TBARs levels than sham-adrenalectomized rats. The effect of adrenalectomy was reverted by the administration of corticosterone but not by that of aldosterone, indicating that glucocorticoids exert a negative role on the regulation of liver TBARs. The effect of these hormones appears to be a permissive one, since the administration of a long lasting ACTH preparation did not reduce liver TBARs. In contrast to that observed in unstressed rats, glucocorticoids appeared to increase liver TBARs in stressed rats. Nevertheless, other alternative explanations are possible. Finally, no evidence for a role of catecholamines in the regulation of hepatic TBARs was found.

Adrenalectomy↗

Effect of morphine administration on rat liver metallothionein and zinc metabolism.

The putative involvement of opioid receptors in rat liver metallothionein (MT) regulation has been studied by means of morphine administration. Rat liver MT levels were significantly increased by morphine (10 mg kg-1). This increase was blocked by the opiate antagonist naloxone (4 mg kg-1), suggesting that the effect of morphine on liver MT could involve opioid receptors. The effect of morphine appears to be mediated, at least in part, by glucocorticoids and catecholamines, inasmuch as the administration of specific receptor blockers, RU 486 (100 mg kg-1) for glucocorticoids and labetalol (5 mg kg-1) for catecholamines, diminished liver MT increase induced by morphine. These results identify a potential mediation mechanism for regulating liver MT levels. The putative role of endogenous opioids on liver MT response to stress was also studied by means of opioid receptor blockers. The effect of stress on liver MT levels was not altered by blockade of opioid receptors with either naloxone (4 mg kg-1) or naltrexone (4 mg kg-1) or diprenorphine (4 and 20 mg kg-1), suggesting that endogenous opioids are not involved in MT response to stress. Zn metabolism was also altered by morphine, as morphine administration increased liver cytosolic Zn and decreased serum Zn levels. In contrast to those found in liver MT, these changes were not naloxone-sensitive. The results obtained with RU 486 and labetalol suggest that the effect of morphine on Zn metabolism was mediated in part by glucocorticoids and catecholamines.

Animals↗

The serum glucose response to acute stress is sensitive to the intensity of the stressor and to habituation.

The reliability of serum glucose concentrations as an index of habituation to chronic stress was evaluated in adult male rats. The glucose response to immobilization was attenuated by six days of previous chronic exposure to the same stressor, the degree of reduction being related to the duration (15 min, 1 hr or 4 hr) of the daily exposure to immobilization. In another experiment, three groups of rats were exposed to one of three stressors (handling plus change of room, restraint in tubes, or immobilization by wood boards), 1 hr daily for 27 days. On day 28, when faced with the same acute stressor to which they were chronically exposed, the rats showed a consistent reduction in glucose response, regardless of the type of stressor used. In addition, in stress-naive rats serum glucose levels were related to the intensity of the stressor as assessed by three independent measures (food intake, body weight changes, and adrenal weight after chronic exposure to the stressor). These data indicate that, under appropriate conditions, glucose levels can be a good index of both the intensity of acute stress experienced by the rats and their habituation to repeated stress.

Adrenal Glands↗

Blockade of opioid receptors with naltrexone inhibits thyrotropin increase after noise stress but does not prevent the decrease caused by immobilization.

The influence of naltrexone-induced opioid receptor blockade on the response of thyrotropin to two different acute stressors was studied in adult male rats. Naltrexone slightly but significantly reduced basal thyrotropin levels and abolished the increase in serum thyrotropin caused by acute noise stress. In contrast, the opioid antagonist did not prevent the decrease in serum thyrotropin caused by another much more severe stressor such as immobilization. The present data offer the first evidence that endogenous opioids could play a stimulatory role in the control of thyrotropin secretion in a presumably physiological condition such as the response to a mild stressor. In addition, factors other than opioids could be involved in the inhibition of thyrotropin secretion under severe stress.

Acoustic Stimulation↗

Liver, brain, and heart metallothionein induction by stress.

To date, stress has been reported to induce metallothionein (MT) synthesis in the liver only. In the present experiment, the effects of food and water deprivation alone or of immobilization stress plus food and water deprivation on liver, brain, and heart MT have been studied in adult male rats. Liver and brain MT levels were increased by immobilization stress as soon as 6 h after the onset of stress. Eighteen hours of immobilization, which is accompanied by food and water deprivation, further increased liver and brain MT levels and significantly increased heart MT content. A specific effect of immobilization was evident in all three tissues, because the effect of food and water deprivation alone was significantly lower than that of immobilization plus starvation. Changes in MT apparently were not related to changes in cytosolic Zn.

Animals↗

Vitamin E-supplemented diets reduce lipid peroxidation but do not alter either pituitary-adrenal, glucose, and lactate responses to immobilization stress or gastric ulceration.

It has been suggested that antioxidant administration to rats would reduce the physiological response to stress. In the present experiment adult male rats were given diets supplemented with vitamin E for one or seven days before they were subjected to immobilization stress. Vitamin E administration reduced hepatic and gastric lipid peroxidation in unstressed rats but did not modify the pituitary-adrenal, glucose and lactose responses to 1 or 18 h immobilization. Similarly, gastric ulceration caused by 18 h immobilization was unaffected by the diets. These results indicate that the inhibition of lipid peroxidation does not modify the response of several, well-known, stress-markers in the rat.

Adrenal Glands↗

On the metallothionein, glutathione and cysteine relationship in rat liver.

Stress and starvation increased liver metallothionein (MT) and decreased liver glutathione (GSH) levels. Serum cysteine plus cystine levels were increased by stress. The exogenous administration of GSH, while not modifying hepatic GSH content, increased liver MT levels in basal and starved rats but not in stressed rats. Liver and serum cysteine levels were increased by GSH administration, a process partially reverted by the irreversible inhibitor of gamma-glutamyl transpeptidase, alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid. Mouse and rat liver MT levels were also increased by buthionine sulfoximine, an inhibitor of GSH synthesis, indicating that GSH is not a necessary precursor of MT. In addition, the hepatic MT content was increased by the administration of cysteine in a dose-response manner. These results suggest that hepatic MT synthesis is elevated by increased cysteine pools, and that MT, GSH and cysteine levels are somehow inter-related. MT, besides GSH, may be contemplated as a putative intracellular reservoir of cysteine in the liver of adult rats.

Animals↗

Chronic administration of clomipramine prevents the increase in serotonin and noradrenaline induced by chronic stress.

The effects of chronic clomipramine administration (15 mg/kg daily for 23 days) on changes in serotonin (5-hydroxytryptamine, 5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and noradrenaline (NA) induced by chronic stress have been studied in the rat brain. Chronic stress increased 5-HT in midbrain, pons and hippocampus, 5-HIAA in frontal cortex, midbrain, pons and hippocampus, and NA in midbrain and striatum. Chronic clomipramine significantly decreased the levels of 5-HT in most regions. In hypothalamus, hippocampus and perhaps in frontal cortex this effect possibly reflects decreased synthesis caused by an action on presynaptic 5-HT receptors. However, in midbrain, pons and striatum decreased 5-HT could not be attributed to a decrease in its synthesis since 5-HIAA also increased. This drug treatment also reduced NA in all regions except the striatum. Nevertheless, conclusions on NA synthesis or turnover cannot be drawn since only NA levels were measured. When administered concurrently, chronic clomipramine prevented the increases in 5-HT, 5-HIAA and NA produced by chronic stress. These results are in good accordance with previous findings showing that chronic antidepressant treatment also prevented behavioural disturbances induced by chronic stress.

Animals↗

Influence of intensity and duration of exposure to various stressors on serum TSH and GH levels in adult male rats.

The effect of stressor intensity and duration of exposure to the stimuli on adrenocorticotropin (ACTH), somatotropin (GH) and thyrotropin (TSH) concentration in serum was studied in adult male Sprague-Dawley rats. The stressors used were noise, restraint in plastic tubes and immobilization on wood boards. The greatest ACTH release was found in immobilized rats and the smallest in noise-exposed animals. The inhibition of GH secretion was related to the intensity of ACTH release in that maximal GH inhibition was observed in immobilized rats and minimal in noise-exposed rats. The TSH response was more complex. Noise increased TSH release at all periods observed (10, 30 and 60 min); the stimulation of TSH release caused by restraint was significant at 30 and 60 min and was always of lesser magnitude than that in response to noise. Finally, immobilization significantly increased TSH levels at 10 min and decreased them at 30 and 60 min. These results suggest that, under appropriate conditions, all hormones studied discriminate between different stressor intensities. However, the complexity of the TSH response to stressors indicates that this hormone is not an adequate index of the stress experienced by the animals.

Adrenocorticotropic Hormone↗

Individual housing does not influence the adaptation of the pituitary-adrenal axis and other physiological variables to chronic stress in adult male rats.

Although the influence of housing conditions on the physiological response to stress has been extensively studied for several years, no attempts have been made to investigate the effect of this variable on the capacity for adaptation to chronic stress. To this end, adult male rats were housed either individually or in groups of four per cage and subjected to 2 hr of daily immobilization stress for 14 days. Housing did not influence any of the physiological variables measured either in unstressed or in stressed rats except the corticosterone response to stress which was higher in individually housed rats. Of the behavioral measures, individual housing significantly decreased defecation rate in the novel environment. Other behavioral measures were not influenced by housing. Chronic stress significantly reduced ambulation but no significant interaction between housing and chronic stress was observed. Taken together, these data indicate that a short period of individual housing did not affect the physiological and behavioral consequences of repeated exposure to chronic stress.

Adaptation, Physiological↗

Comparison of crowding and food restriction effects on growth, body weight gain and endocrine status in the rat.

The present work compares the effects of post-weaning crowding and those of food restriction on growth, body weight gain and the levels of several hormones, in male Sprague-Dawley rats. Crowding resulted in reduced food intake and diminished body weight gain. Rats daily receiving the same amount of food as that eaten by crowded rats (food-restricted group) showed similar body weight gain as crowded rats, but higher growth rate. Neither crowding nor food restriction altered the pituitary-adrenal axis. In contrast, both treatments decreased serum insulin, growth hormone (GH), somatomedin C (Sm-C) and thyroid-stimulating hormone (TSH) as compared to control rats. The reduction of GH and Sm-C levels was similar in crowded and food-restricted rats but that of TSH was higher in food-restricted, rather than in crowded rats. The present data indicate that the effects of crowding could only be partially explained by the concomittant reduction of food intake and that the serum levels of the hormones studied could not explain the differences between the crowded and food-restricted rats with regard to growth.

Animals↗

Lack of effect of alpha-tocopherol and ascorbic acid on the response of some physiological variables to immobilization stress in rat.

The effect of alpha-tocopherol or ascorbic acid jointly and separately on the seric levels of adrenocorticotropin (ACTH) and corticosterone has been studied. ACTH response to stress is similar in all groups, whereas the corticosterone response is higher in the animals treated with alpha-tocopherol. Neither lactate response nor gastric ulceration caused by stress was influenced by the administration of alpha-tocopherol and/or ascorbic acid. These results suggest that free radicals might not be implicated in the control of the physiological response to stress.

Adrenocorticotropic Hormone↗

Forced swimming test in rats: effect of desipramine administration and the period of exposure to the test on struggling behavior, swimming, immobility and defecation rate.

The effect of desipramine administration and the duration of the daily exposure to forced swimming on some variables has been studied in adult male rats. Desipramine administration (15 mg/kg) significantly increased struggling behavior in the first and second 5-min periods of a single exposure to forced swimming. Swimming was reduced in the first 5 min and remained unchanged thereafter. Immobility was decreased in the second and the third 5-min periods. After a pre-exposure to forced swimming for 15 min the day before, the drug was effective in increasing struggling behavior and reducing immobility during a subsequent 5-min test. Swimming was not modified. Daily exposure to forced swimming for 3 days caused a decline in struggling behavior and swimming, while increasing immobility and the defecation rate. The duration of daily exposure to forced swimming did not alter the changes in the variables measured. The present results indicate that a one-day test can be used to discriminate between saline- and desipramine-treated rats, and that struggling behavior could be a reliable measure of the positive action of antidepressants. The finding that behavioral changes over the 3 days were independent of the duration of exposure to swimming argues against the interpretation of the results which suggest that the responses are caused by the appearance of a behavioral despair state, and suggests that these behaviors might be trait-markers in the rat. In addition, the changes in struggling behavior and immobility over the 3 days cannot be attributed to a behavioral adaptation to the test because the defecation rate increased rather than decreased during successive forced swimming tests.

Animals↗

Previous chronic chlorimipramine treatment did not modify some physiological responses to acute and chronic stress in rats.

The effects of previous chronic administration of the tricyclic antidepressant drug chlorimipramine (CMI) on some physiological responses of adult male rats to stress has been studied. CMI significantly reduced food intake and body weight gain, but did not alter either adrenal weight or basal serum corticosterone levels. Corticosterone response to 1 h of immobilization stress was the same in saline and CMI-treated rats. When the rats previously treated with CMI were subjected to chronic immobilization stress, it was found that the drug did not alter the anorexic effects of the stressor, but reduced the rate of adaptation of adrenocorticotropin response to stress. These data indicate that previous chronic CMI administration does not prevent changes in the secretory activity of the pituitary-adrenal system or the reduction of food intake and body weight caused by strong stressors.

Adrenal Glands↗

Chronic stress increases serotonin and noradrenaline in rat brain and sensitizes their responses to a further acute stress.

The effects of 1 h/day restraint in plastic tubes for 24 days on the levels of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), tryptophan (TP), and noradrenaline (NA) in six regions of rat brain 20 h after the last restraint period were investigated. The levels of 5-HT, 5-HIAA, and NA but not TP increased in several regions. The effects of 1 h of immobilization on both control and chronically restrained rats were also studied. Immobilization per se did not alter brain 5-HT, 5-HIAA, and TP levels, but decreased NA in the pons plus medulla oblongata and hypothalamus. However, immobilization after chronic restraint decreased 5-HT, increased 5-HIAA, and decreased NA in most brain regions in comparison with values for the chronically restrained rats. We suggest that chronic restraint leads to compensatory increases of brain 5-HT and NA synthesis and sensitizes both monoaminergic systems to an additional acute stress. These changes may affect coping with stress demands.

Animals↗

Physiological role of glucocorticoids on rat serum and liver metallothionein in basal and stress conditions.

Serious contradictions exist at present in our understanding of the physiological role of glucocorticoids on the synthesis of the metal-binding protein, metallothionein (MT). In addressing this problem, we have examined in vivo the role of glucocorticoids on liver and serum MT levels in the rat under a spectrum of experimental conditions. The experiments confirm that stress has a major positive effect on hepatic MT levels. It was found that adrenocorticotropic hormone (ACTH) administration has an inhibitory effect on hepatic MT levels in response to restraint stress and that adrenalectomy (ADX) leads to an increase in basal MT levels and in MT levels in response to acute and chronic immobilization stress. Similar results followed treatment with the glucocorticoid receptor blocker, RU 486. The effect of ADX was abolished by corticosterone replacement. The relations found among hepatic MT, serum MT, and glucocorticoid concentrations indicate that in some circumstances glucocorticoids have a permissive role in mobilizing MT from tissues to serum and that in physiological conditions corticosterone has an inhibitory role in the maintenance of hepatic MT levels.

Adrenalectomy↗