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Biomedical subjects

A Armario

Publications and source records attributed to A Armario.

At least 55 records · Page 3Linked to original sources

Inhibition of catecholamine synthesis with alpha-methyl-p-tyrosine apparently increases brain serotoninergic activity in the rat: no influence of previous chronic immobilization stress.

The functional relationship between brain catecholamines and serotoninergic function was studied in stress-naive and chronically immobilized rats after blockade of catecholamine synthesis with alpha-methyl-p-tyrosine (alpha MpT). The levels of noradrenaline (NA), serotonin, and 5-hydroxyindole acetic acid (5-HIAA) in pons plus medulla, brainstem, hypothalamus, hippocampus, and frontal cortex, and those of 3-methoxy, 4-hydroxyphenile-tileneglicol sulphate (MHPG-SO4) in the hypothalamus were measured by HPLC. Chronic immobilization (IMO) resulted in higher NA levels in pons plus medulla and hypothalamus, the latter area (the only one in which the NA metabolite was determined) also showing slightly elevated MHPG-SO4 levels as compared to stress-naive rats. Chronic IMO did not alter either serotonin or 5-HIAA levels, but acute stress consistently increased 5-HIAA levels in all areas, independently of previous chronic stress. Administration of alpha-MpT drastically reduced NA and increased 5-HIAA levels in all brain regions excepting the frontal cortex. The effect of the drug on serotoninergic function was not altered by previous chronic exposure to IMO. These data suggest that the noradrenergic system appears to exert a tonic inhibitory effect on serotoninergic activity in the brain, with the intensity of the effect depending on the brain area studied. In addition, chronic stress does not appear to alter the functional relationship between noradrenergic and serotoninergic activities, although interactions might exist in more restricted brain areas; this deserves further study.

Acute Disease↗

Comparison of the behavioural and endocrine response to forced swimming stress in five inbred strains of rats.

Some inbred strains of rats showed behavioural differences in the forced swimming test, which is considered a putative animal model of depression. In the present work, the behavioural and physiological responses to forced swimming were studied in male and female rats of five inbred strains of rats: Brown-Norway (BN), Fischer 344 (FIS), Lewis (LEW), Spontaneously Hypertensive (SHR) and Wistar-Kyoto (WKY). Physiological measures were aimed at characterizing emotional reactivity, a very important issue which has usually been approached by studying a single endocrine system, and its relationship to the forced swimming behaviour. The four indices of reactivity to stress used were serum glucose, ACTH, corticosterone and prolactin. No behavioural differences between sexes were observed in the forced swimming test. In addition, BN and WKY rats showed passive behaviour compared with the other three strains, the FIS strain being the most active. Whereas only minor differences were found in the resting levels of the variables studied with regard to either sex or strain, pituitary-adrenal (PA) and glucose responses to 15 min forced swimming differed among sexes and strains. Stress-induced hyperglycaemia was lowest in WKY and highest in SHR, being lower in females than in males. The lowest ACTH and corticosterone responses to forced swimming were observed in LEW and the highest in FIS. Female rats showed a clearly higher PA response to stress in all strains. Prolactin response to stress was very similar between sexes and strains. It might thus be concluded that: (i) there are important inter-strain differences in the forced swimming behaviour, with no differences between sexes; (ii) the various physiological indices of emotional reactivity follow a different trend and no warranted conclusion on differences in emotional reactivity should be based upon a single endocrine system or even only upon physiological measures; (iii) we cannot be sure, therefore, whether or not there are differences in emotionality between the strains studied in spite of well-established inter-strains differences in the forced swimming behaviour.

Adrenocorticotropic Hormone↗

Effects of chronic stress on food intake in rats: influence of stressor intensity and duration of daily exposure.

The effect of exposure to chronic intermittent stressors of differing intensities [handling, restraint, and immobilization (IMO)] and daily duration (15, 60, and 240 min of IMO) on changes in food intake was studied in adult male rats. Whereas handling did not caused anorexia, restraint slightly reduced food intake and IMO drastically reduced it. The effects were very similar after the 7th and 27th day of exposure to the stressors. Fourteen days of chronic IMO (2 h daily) resulted in decreased food intake as measured on days 1, 10, and 14 of treatment, the inhibition being slightly greater after the first stress session. The circadian rhythm of food intake, expressed as a percent of the total food eaten in a 24 h period, was found to be almost unaffected by chronic IMO, although IMO rats appeared to satiate sooner than control rats. Exposure of rats to chronic IMO (7 days) for 15, 60, and 240 min daily reduced food intake to the same extent in all IMO groups. Taken together, these results suggest that: a) the magnitude of the changes in food intake after chronic exposure to stressors is closely related to their intensity, and b) a severe stressor such as IMO reduces food intake to a certain level that was independent on its daily duration. After repeated exposure to the same stressor, only a slight tendency to recover normal food intake was observed.

Adrenal Glands↗

Direct evidence for chronic stress-induced facilitation of the adrenocorticotropin response to a novel acute stressor.

The ACTH response to CRF and the role of glucocorticoids on the pituitary-adrenal responsiveness to acute stressors after a period of chronic stress were assessed in Sprague-Dawley rats. After chronic immobilization (IMO) an enhanced ACTH response to CRF administration was observed. In another experiment, control and chronic IMO rats were adrenalectomized (ADX) or sham-adrenalectomized (SHAM) and 2 days later killed in resting conditions or after having been subjected to acute IMO or tail-shock for 30 min. Chronic IMO increased basal corticosterone but not adrenocorticotropin (ACTH) levels in SHAM rats. As expected, ADX increased ACTH levels in all conditions. In response to the novel acute stressor (shock), ACTH levels were drastically dependent on the presence of corticosterone: thus, whereas in SHAM rats chronic IMO reduced the ACTH response to shock, in ADX rats a clear enhancement of the ACTH response to shock was observed in chronic IMO rats. In order to demonstrate that, in our experimental conditions, chronic stress also induces down-regulation of glucocorticoid receptors in the hippocampus, an additional experiment was done: rats subjected chronically to IMO or administered 5 mg corticosterone (B) were adrenalectomized and killed 20 h later under basal conditions. Both chronic IMO and chronic B administration decreased glucocorticoid type II binding in the hippocampus. From these results, it is concluded that chronic IMO induces facilitation of the ACTH response to novel acute stressors which is uncovered after corticosterone removal.

Adrenalectomy↗

The effect of acute and chronic ACTH administration on pituitary-adrenal response to acute immobilization stress. Relationship to changes in corticosteroid-binding globulin.

The effect of single and chronic ACTH administration on serum levels of the corticosteroid-binding globulin (CBG) and pituitary-adrenal (PA) responsiveness to acute immobilization (IMO) stress was studied in adult Sprague-Dawley rats. Single ACTH administration significantly reduced CBG levels but did not alter PA response to acute IMO. Chronic ACTH administration caused a greater fall in CBG than single ACTH administration and blunted PA response to IMO. The effect of chronic ACTH administration on CGB levels recovered 2 days after the last administration, but the ACTH response to IMO was normal only by day 7 after the last ACTH injection. The present data indicate that ACTH administration to rats reduced CBG levels and impaired PA response to acute stress, but impaired PA responsiveness cannot be solely attributed to changes in CBG.

Adrenocorticotropic Hormone↗

Effects of diazepam and desipramine in the forced swimming test: influence of previous experience with the situation.

The effects of desipramine and diazepam on the behavior of rats in the forced swimming test were studied. Desipramine significantly enhanced struggling behavior, the intensity of its effect being greater in rats previously exposed to the forced swimming test for 1 or 4 days before drug administration. The effect of desipramine on immobility was significantly only in rats previously exposed to the test. Acute diazepam administration did not modify the behavior of rats in the test. Chronic administration (6 days) of two different doses of diazepam did not alter the behavior of rats in the forced swimming test, but significantly decreased the defecation rate, suggesting that the drug was effective as an anxiolytic. The present results suggest that the behavior of rats in the forced swimming test might be related to mood states rather than to fear/anxiety and that efficacy of the test to detect antidepressant activity might be enhanced by repeated exposure of the rats to the situation.

Animals↗

Chronic stress reduces serum but not liver metallothionein response to acute stress.

Rats subjected to chronic immobilization stress showed a reduced serum metallothionein (MT) response to acute immobilization stress compared to nonchronically stressed rats. In contrast, liver MT response to acute immobilization stress was not influenced by previous chronic immobilization stress. These results suggest that serum MT levels are likely under endocrine regulation and that they do not reflect directly liver MT levels. Instead it appears that both MT pools are regulated differently. The fact that liver MT is resistant to adaptation to chronic stress may be related to its physiological function.

Acute Disease↗

Chronic stress induced changes in LH secretion: the contribution of anorexia associated to stress.

The effects of chronic intermittent immobilization (IMO) on serum LH levels of adult male rats were studied. Chronic IMO (2 h daily for 13 days) did not alter basal LH levels, but abolished the LH response to acute stressors (IMO and tailshock). The inhibition of LH caused by acute exposure to IMO for 4 or 18 h was similar in control and chronic IMO rats. Also the LH response to exogenous LHRH administration was normal in chronically stressed rats. When a group of rats eating the same amount of food as that eaten by immobilized rats was introduced (pair-fed), an inhibition of LH response to acute stressors quite similar to that found in chronic IMO rats was observed. These data indicate that chronic stress-induced inhibition of LH release caused by short-term exposure to acute stressors was located above the pituitary and was mainly due to anorexia accompanying daily exposure to the stressor.

Analysis of Variance↗

Role of somatostatin in the acute immobilization stress-induced GH decrease in rat.

In the present work we have investigated to what extent somatostatin (SRIF) release from median eminence (ME) is affected by stress immobilization (IMO) in unanesthetized rats stereotaxically implanted with a push-pull cannula (PPC). One week after implantation, the ME was perfused with artificial cerebrospinal fluid for 1 hour in basal, stress and recovery conditions respectively. Samples were collected every 15 min and SRIF was measured by RIA. In another group of animals, a jugular cannula was inserted the day before and plasma samples were taken off simultaneously with the ME perfusate for GH and SRIF analysis respectively. SRIF release from the ME is rapidly (15 min) and significantly increased (58 +/- 11 vs 28 +/- 5 pg/15 min; n = 7; P < 0.01) in rats bearing only PPC. Intriguingly, animals bearing a jugular catheter plus a PPC showed no increase in SRIF release during the first 15 min of IMO in spite of a striking decrease of plasma GH (27.2 +/- 3.8 vs 3.6 +/- 1.3 ng/ml; n = 6; P < 0.001) observed at this time. However, in spite that the animals responded with a significant increase in SRIF, the response was later and more reduced than in animals without jugular cannula. Since our two rat groups--as result of jugular cannula surgery 24 hours before--showed differences such as a food intake, body weight gain, plasma GH levels and basal SRIF release, we think that these differences could explain the modifications in the regulatory mechanisms involved in GH control under acute stress.

Animals↗

Effects of chronic immobilization stress on GH and TSH secretion in the rat: response to hypothalamic regulatory factors.

The effect of chronic immobilization (2 h/day) for 13 days on basal and stress levels of GH and TSH, and their response to various hypothalamic regulatory factors was studied in male Sprague-Dawley rats. Chronic immobilization (IMO) resulted in reduced serum TSH levels in stress situations but not in resting conditions. GH secretion was inhibited both in resting and stress situations. Chronic IMO impaired both GH and TSH responses to GRH and TRH, respectively, but also to another peptide (VIP) stimulatory for the two hormones. Whereas somatostatin administration inhibited GH secretion in control but not in chronic IMO rats, its inhibitory effect on TSH was slight and similar in the two experimental groups. The present results suggest that chronic exposure to a severe stressor such as IMO alters GH and TSH secretion, at least in part by changes in the response of the pituitary to the hypothalamic regulatory factors. The actual influence of chronic IMO on the release of these peptides into the median eminence remains to be studied.

Animals↗

Effect of regularity of exposure to chronic immobilization stress on the circadian pattern of pituitary adrenal hormones, growth hormone, and thyroid stimulating hormone in the adult male rat.

Circadian variation of serum levels of adrenocorticotropin hormone (ACTH), corticosterone, growth hormone (GH), and thyroid-stimulating hormone (TSH) were studied in three groups of adult male rats exposed to chronic intermittent immobilization stress (IMO) for 2 hr daily under different schedules. IMO resulted in reduced food intake, body weight loss, and increased adrenal weight. ACTH levels were not affected but corticosterone levels were increased in all IMO rats as compared to control ones during the diurnal phase of the circadian cycle. IMO decreased serum GH and TSH levels but the circadian pattern of secretion was influenced in a complex way depending on the specific pattern of daily exposure to IMO. Differences observed between the IMO groups were not caused by differences in food intake because its circadian rhythm was very similar in all IMO groups. These results suggest that regularity of exposure to immobilization alters in a complex fashion circadian GH and TSH rhythms.

Adrenal Cortex Hormones↗

Evidence for the involvement of serotonin in acute stress-induced release of luteinizing hormone in the male rat.

The influence of serotonin on luteinizing hormone (LH) release caused by exposure to two acute stressors differing in their intensity (restraint in tubes and immobilization in woodboards) was studied in adult male rats. Inhibition of serotonin synthesis with p-chlorophenylalanine (PCPA) significantly abolished LH release caused by immobilization (IMO). Administration of the serotonin antagonists mianserine and methiothepin also eliminated LH release caused by IMO without altering basal LH levels. These data represent the first evidence that a classical neurotransmitter (serotonin) is involved in LH release caused by stress in the rat.

Acute Disease↗

Chronic but not acute exposure to stress is associated with hypothalamic vasoactive intestinal polypeptide (VIP) release into median eminence.

The influence of stress on hypothalamic VIP release into the pituitary portal blood has not been assessed at present despite the fact that this peptide has been implicated in the control of several pituitary hormones and especially in the release of prolactin (PRL) caused by stress. In the present work the effect of stress on the in vivo release of VIP into the pituitary portal blood of male rats was evaluated by means of push-pull perfusion (PPP) of median eminence (EM). VIP content in the PPP liquid was successfully measured and their levels agree well with pituitary portal blood levels measured by other authors. Whereas plasma PRL levels strongly increased during acute immobilization (IMO), no changes in VIP secretion into the ME were observed. VIP release into the ME was also unaffected by exposure to ether. In contrast, in chronically immobilized rats a significant increase in VIP release into the ME was obtained in response to acute IMO. The present data argue against a major role of hypothalamic VIP in PRL release caused by acute stress and show that chronic stress qualitatively alters the signal of hypothalamic VIP to the pituitary.

Animals↗

Behavioral and neurochemical changes in response to acute stressors: influence of previous chronic exposure to immobilization.

The effect of daily (2 h) exposure to immobilization (IMO) for 15 days on the behavioral and neurochemical responses of adult male rats to acute stress caused by 2-h IMO or 2-h tail-shock was studied. The brain areas studied were frontal cortex, hippocampus, hypothalamus, midbrain, and pons plus medulla. Chronic exposure to IMO did not alter noradrenaline (NA), 3-methoxy,4-hydroxyphenyletileneglycol-SO4 (MHPG-SO4), serotonin, or 5-hydroxindoleacetic acid (5-HIAA) concentrations in any brain area as measured approximately 20 h after the last exposure to IMO. Exposure to behavioral tests did not modify neurochemical variables except NA levels in the hypothalamus of nonchronically stressed (control) rats. Both exposure to 2-h IMO or 2-h shock significantly decreased NA levels in hypothalamus and midbrain of nonchronically stressed rats. These decreases in response to the two acute stressors were not observed in chronically stressed rats. However, MHPG-SO4 levels increased to the same extent in control and chronically stressed rats after exposure to the acute stressors. Likewise, increased 5-HIAA concentrations observed in response to acute stressors were similar in control and chronically stressed rats. The inhibition of activity (areas crossed and rearing) in the holeboard caused by acute IMO was less marked in rats previously exposed to the same stressor than in control rats, but the response to shock was similar. In the forced swim test, acute IMO decreased struggling in control rats but tended to increase it in chronically stressed rats. The response to shock followed the same pattern as that to IMO, although it was slight.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Inhibition of catecholamine synthesis depresses behavior of rats in the holeboard and forced swim tests: influence of previous chronic stress.

Catecholaminergic pathways in the brain are activated during stress and are presumably involved in the control of physiological and behavioral changes triggered by stress. When repeatedly stressed, adaptive changes have been observed in catecholaminergic activity in the brain. In the present experiment, it was assessed whether or not chronic exposure to immobilization (IMO) altered the influence of catecholamines on behavior in the holeboard and forced swim test by administering alpha-methyl-p-tyrosine (an inhibitor of catecholamine synthesis). Adult Sprague-Dawley rats were used. Chronic stress amortiguated the inhibitory effect of acute IMO on some but not all behaviors in the two tests. Whereas previous chronic IMO exacerbated the effects of the drug on struggling and immobility in the forced swim test, no change in response to the drug as a consequence of chronic IMO was observed in the holeboard test. The present data suggest that chronic IMO-induced changes in the catecholaminergic control of some behaviors might be related to depression-like states in rats. The actual physiological meaning of these changes and the specific receptors involved remain to be elucidated.

Animals↗

Negative feedback of corticosterone on the pituitary-adrenal axis is maintained after inhibition of serotonin synthesis with parachlorophenylalanine.

The role of the serotonergic transmission on the negative feedback of corticosterone on the pituitary-adrenal (PA) axis was studied in adult male rats. Animals were given p-chlorophenylalanine (PCPA) and 24 h later were administered corticosterone, 2 h before being subjected to 20 min of noise stress. The main results were as follows: First, PCPA administration increased resting levels of both corticotropin (ACTH) and corticosterone but did not alter PA response to noise stress; second, ACTH response to stress was eliminated in rats given PCPA; third, corticosterone reduced ACTH levels in nonstressed rats only and this effect was maintained after PCPA administration. Taken together, the present results suggest a mediator role for serotonin in the noise-stress-induced PA hormone release but no role in the negative feedback of corticosterone on the PA axis.

Adrenocorticotropic Hormone↗

Metallothionein-I induction by stress in specific brain areas.

The distribution of metallothionein-I (MT) in several areas of the brain and its induction by immobilization stress has been studied in the rat. MT content was highest in hippocampus and midbrain and lowest in frontal cortex and pons plus medulla oblongata. Immobilization stress for 18 hours (which was accompanied by food and water deprivation) significantly increased MT levels in the frontal cortex, pons plus medulla oblongata and hypothalamus, but not in midbrain and hippocampus. The effect of stress on MT levels was specific as food and water deprivation along had no significant effect on MT levels in any of the brain areas studied. The effect of stress on MT levels was independent of changes in cytosolic Zn content; this was generally unaffected by stress or food and water deprivation but decreased in pons plus medulla oblongata from stressed rats. The results suggest that MT is induced more significantly in the brain areas that are usually involved in the response of animals to stress.

Analysis of Variance↗

Influence of various acute stressors on the activity of adult male rats in a holeboard and in the forced swim test.

The effects of various acute stressors on the activity of adult male rats in a holeboard and in the forced swim test were studied. When tested immediately or 24 h after 1 h exposure to noise, restraint in tubes or tail shock, no changes in either defecation rate or activity in the holeboard were observed. In contrast, immediately after 1 h immobilization in wood-boards, a reduction of the number of areas crossed and the number of head-dips was found. The inhibitory effect of immobilization on head-dips persisted 24 h later. The behavior of the rats in the forced swim test was classified into three categories: struggling, mild swim and immobility. The changes in behavior were critically dependent on the type of stressor, and more specifically on its intensity, that was evaluated with three different physiological parameters (serum prolactin, corticosterone and glucose levels). Thus, if tested immediately after stress, noise did not alter the response of the rats, restraint in tubes and tail shock-reduced immobility, and the latter stressor increased mild swim. In the second experiment, immobilization in wood-boards reduced struggling. Twenty-four hours after stress, noise, restraint in tubes or tail shock were without effect, but immobilized rats showed increased immobility and reduced mild swim activity. The present data clearly indicate that behavior of rats in a holeboard and in a forced swim situation are not related, and that acute stress could have a differential effect on the various categories of behavior in a forced swim situation.

Animals↗