Biomedical subjects

A Armario

Publications and source records attributed to A Armario.

At least 37 records · Page 2Linked to original sources

PubMed1999

Defective ACTH response to stress in previously stressed rats: dependence on glucocorticoid status.

The effect of previous exposure to stress on the pituitary-adrenal response to a further stress was characterized in rats with different glucocorticoid status: sham-operated rats (Sham), adrenalectomized (ADX) rats, and ADX rats supplemented with a low corticosterone (B) dose in the drinking saline (ADX + B). Previous exposure of Sham rats to 1 h of immobilization (Imo) reduced, 2 h later, the ACTH response to a second severe stressor (Imo) but not to a less severe stressor (tail shock). In ADX rats, previous Imo totally suppressed the ACTH response to Imo or to shock. In ADX + B rats the response to shock was blocked and that to Imo tended to be lower. These changes were not explained by depletion of adenohypophysial ACTH stores. After previous Imo, reduced response to corticotropin-releasing factor was observed in Sham and ADX + B, but not in ADX, rats. Taken together, the present results suggest that the reduced ACTH response of previously stressed rats to a second severe stress is observed in the presence and absence of glucocorticoids, but the main site at which such inhibition occurs might be critically dependent on the glucocorticoid status.

Adrenalectomy↗

PubMed1999

Abnormalities of hypothalamic-pituitary-adrenal and hypothalamic-somatotrophic axes in Fawn-Hooded rats.

Fawn-Hooded (FH) rats show central and peripheral abnormalities in serotoninergic functions and have attracted attention as an animal model of some pathologies, including depression and hypertension. In addition, these rats show a reduced growth rate. As the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in both depression and hypertension, and the hypothalamic-somatotrophic (HSM) axis has a major role in growth, these two endocrine axes were characterised in FH rats as compared with outbred Sprague-Dawley (SD) rats in basal conditions. FH rats showed normal serum ACTH and corticosterone concentrations, but reduced serum corticosterone binding capacity. At a central level, normal expression of mRNA for glucocorticoid type II receptors in the hippocampal formation and mRNA for corticotrophin-releasing factor (CRF) in the paraventricular nucleus of the hypothalamus were observed in FH rats, whereas expression of mRNA for CRF in the central nucleus of the amygdala was enhanced compared with the expression in SD rats. Serum GH concentrations were normal in FH rats, IGF-I tended to be lower, and mRNA for somatostatin (SRIF) in the periventricular nucleus of the hypothalamus was significantly lower in FH rats than in SD rats. The reduced SRIF gene expression in rats with normal or slightly reduced GH and IGF-I, respectively, might be secondary to a defective central and peripheral response to IGF-I, compatible with the reduced growth of FH rats. The present results suggest that FH rats have abnormalities in both HPA and HSM axes that might be related to some of their physiopathological characteristics.

Adrenocorticotropic Hormone↗

PubMed1998

IL-6 deficiency leads to increased emotionality in mice: evidence in transgenic mice carrying a null mutation for IL-6.

The role of interleukin-6 (IL-6) on emotional behavior was studied in two experiments using transgenic mice carrying a null mutation for IL-6 (IL-6(-/-)). In the first experiment, IL-6(-/-) mice were compared with the two wild-type strains contributing to the genetic background of the transgenic mice, namely C57BL/6J and 129/SvJ, as well as with the F2 offspring of C57BL/6J x 129/SvJ mice. The two parental strains differed substantially in terms of emotional reactivity, suggesting that the F2 offspring were more appropriated for analyzing the effect of the null mutation. IL-6(-/-) mice showed lower levels of ambulation in the holeboard, and lower levels of exploration of the open arms of the plus-maze, than the wild-type F2 C57BL/6J x 129/SvJ mice. In the second experiment, IL-6(-/-) mice were backcrossed for 10 generations to C57BL/6J mice to decrease the uncertainty of the effect of the genetic background, and when compared with wild-type C57BL/6J mice in the holeboard and the plus-maze, the same results were obtained. Therefore, IL-6(-/-) mice seem to be more emotional than their appropriate controls, suggesting that the major cytokine IL-6 is involved in the control of emotionality.

Animals↗

PubMed1998

The effect of chronic administration of antidepressants on the circadian pattern of corticosterone in the rat.

Although antidepressant administration has been reported to alter the pituitary adrenal (PA) axis, the results are puzzling. In the present work, two possible factors contributing to these contradictory results were studied in adult male Sprague-Dawley rats: (i) the type of antidepressant and (ii) the time of day at which samples were taken. Samples were taken under nonstressful conditions. In expt 1, the acute effects of two doses (10 and 20 mg/kg) of the tricyclics clomipramine (CMI), desipramine (DMI) and imipramine (IMI), and the non-specific monoamine oxidase inhibitor (MAOI) phenelzine were studied. Only phenelzine increased plasma corticosterone with the low dose, whereas phenelzine and DMI increased plasma corticosterone with the high doses when measured 30 min after drug administration. In a second experiment, it was observed that after 12 daily doses of the drugs (20 mg/kg), all drugs increased plasma corticosterone at 30 min after the last drug administration. When the circadian pattern of corticosterone was studied in the same experiment, starting on the day after the last drug administration, a significant interaction of drug by time of day was found. Drugs caused changes in the normal levels of plasma corticosterone at certain times and DMI, IMI and phenelzine reduced the number of rats showing the normal corticosterone peak at 1900 hours. No significant effect of drugs on corticosteroid-binding globulin (CBG) was found. In a third experiment, phenelzine and IMI were administered as before, but samples were taken at several times both on the day of the last drug administration and on the following day. The two drugs altered the normal circadian pattern of corticosterone in a somewhat different way, but both caused a reduction of the corticosterone peak at lights off on the day after the last drug administration. The normal relative thymus weight observed in all groups (exp. 2) suggests that the overall biological activity of corticosterone was probably not affected by antidepressants. The present results indicate that most antidepressants are able acutely to activate the PA axis after repeated administration in a similar way or even more-strongly than after the first administration, and that some of these drugs alter normal circadian pattern of corticosterone. No evidence for decreased resting PA activity was found in antidepressant-treated rats.

Animals↗

PubMed1998

Chronic immobilization stress appears to increase the role of dopamine in the control of active behaviour in the forced swimming test.

Previously, we have demonstrated that chronic exposure to immobilization (IMO) did not modify the influence of catecholamines on active behaviour of rats in the holeboard, but clearly increased the role of these amines in the forced swimming test (FST). In the present experiment, it was studied whether or not chronic IMO altered the role of dopamine in the two tests. Adult male Sprague-Dawley rats were left either undisturbed or subjected daily to 2 h of IMO stress for 12 days. On the following day, half of the rats were administered saline and the others the dopamine antagonist haloperidol (0.5 mg/kg). Then the rats remained undisturbed in the animal room (controls) or were subjected to acute IMO for 2 h. Finally, all animals were exposed consecutively to the holeboard (4 min) and the FST (5 min). In non-chronically stressed rats, acute IMO depressed behaviour in the holeboard but not in the FST. In chronic IMO rats the inhibitory effect of acute IMO on holeboard activity was slightly reduced as compared to controls. Acute IMO increased struggling in rats previously exposed to chronic IMO but did not alter struggling in non-chronically stressed rats. Whereas the inhibition caused by haloperidol treatment in the active behaviour of rats in the holeboard was not altered by chronic IMO, the inhibitory effect of haloperidol in the active behaviour of rats in the FST was greater after chronic IMO, particularly in rats also subjected to acute IMO. These data suggest that chronic IMO stress potentiates the role of dopamine in a specific behavioural task such as the FST and adds support to the previously published data demonstrating enhanced behavioural and neurochemical responses to dopamine-related drugs after chronic stress.

Animals↗

PubMed1998

Glucocorticoid negative feedback on the HPA axis in five inbred rat strains.

The aim of the present work was to study the influence of altering glucocorticoid negative feedback on both basal activity of the hypothalamic-pituitary-adrenal (HPA) axis and its response to acute stress (tail shock) in five inbred rat strains known to differ in some depression-like behaviors: Brown Norway (BN), Fischer 344 (F344), Lewis (Lew), spontaneously hypertensive (SHR), and Wistar-Kyoto (WKY) rats. Two complementary approaches were used: 1) enhancement of negative feedback by administration of 0.05 and 0.2 mg/kg dexamethasone (Dex) and 2) attenuation of negative feedback by pharmacological adrenalectomy (PhADX). The results indicate that 1) Lew rats consistently show adrenocorticotropic hormone (ACTH) and corticosterone hyporesponsiveness to stress, 2) interstrain differences in the effect of Dex on the HPA axis were very weak and not related apparently to differences in the metabolism of the steroid, 3) the suppressive effect of the highest dose of Dex on basal corticosterone levels was lower in BN rats than in the other strains, and 4) after PhADX, an increase in ACTH levels was observed in response to acute stress in BN, F344, and WKY but not in Lew and SHR rats, suggesting possible interstrain differences in pituitary sensitivity to neural stimuli induced by stress. In summary, our results indicate that there are differences among the strains with regard to both 1) the suppressive effect of Dex on the HPA axis, BN rats showing a certain degree of resistance, and 2) the capability of PhADX rats to respond to acute stress, which suggests a defective release of ACTH in Lew and SHR rats. The biological meaning of these alterations of corticosteroid negative feedback among the five inbred strains studied remains to be established.

Adrenal Glands↗

PubMed1997

Are Wistar-Kyoto rats a genetic animal model of depression resistant to antidepressants?

Wistar-Kyoto rats are reported to be very passive in the forced swimming test. In addition, they did not respond to acute administration of either desipramine or 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). In the present experiment, it was studied whether or not they respond to acute and chronic administration of imipramine and the possible relationship to down-regulation of beta-adrenoceptors and 5-HT1 and 5-HT2 receptors. Sprague-Dawley and Brown-Norway rats were included in the study as it has been previously demonstrated that the two strains respond to acute desipramine and 8-OH-DPAT administration. Whereas acute administration of imipramine (15 mg/kg, three times in a 24 h period) significantly increased struggling and reduced immobility in Sprague-Dawley and Brown Norway rats, Wistar-Kyoto rats failed to respond to the drug. After chronic treatment with imipramine (13 days plus the acute imipramine treatment at the end of the treatment period), the three strains showed a positive response that was always significantly greater than the response to acute administration, but which was much lower in Wistar-Kyoto than in the other two strains. Down-regulation of both beta-adrenoceptors and 5-HT2 receptors was observed 24 h after the forced swimming test in acutely and chronically imipramine-treated rats of the three strains, except that in Sprague-Dawley rats beta-adrenoceptors did not change after acute imipramine. No significant decrease in 5-HT1 binding sites was observed in any strain. Acute imipramine administration caused a similar anorexia in Wistar-Kyoto as in the other strains and at least the same level of down-regulation of beta-adrenoceptors and 5-HT2 receptors. In addition, serum imipramine levels on the day after the last drug administration were higher in Wistar-Kyoto than in the other two strains. All these data suggest that the subsensitivity to imipramine observed in Wistar-Kyoto rats: (i) can not be primarily explained by pharmacokinetic differences, and (ii) does not appear to be related to the monoaminergic systems. Wistar-Kyoto rats might be therefore not only a good animal model of depressive-like (passive) behavior, but also a model of resistance to antidepressants which could be used to investigate the neurobiological basis of such resistance, which is also observed in some depressed patients.

Animals↗

PubMed1997

Brain corticotropin-releasing factor immunoreactivity and receptors in five inbred rat strains: relationship to forced swimming behaviour.

In the present work we studied the relationship between behaviour in the forced swimming test (FST), a test that presumably measures depressive-like behaviour in rodents, and central corticotropin-releasing factor (CRF) concentration and binding in five strains of rats. The strains were: Brown-Norway (BN), Fisher (FIS) 344, Lewis (LEW), spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The FST data corresponding to the pretest showed significant inter-strain differences in both struggling and immobility: BN and WKY rats displayed lower levels of struggling and longer periods of immobility, LEW and SHR rats showed intermediate levels, and FIS rats were the most active. The results of the pretest were roughly similar to those observed in the test, the activity of WKY being extremely low. The CRF binding revealed significant inter-strain differences in prefrontal cortex and hippocampus, but not in cerebellum, pons-medulla or hypothalamus: in the prefrontal cortex, BN and FIS rats showed greater CRF binding than LEW, SHR and WKY rats; in the hippocampus BN rats showed higher levels of CRF binding than the other strains. The study of CRF content in various brain areas revealed inter-strain differences in prefrontal cortex and pons-medulla, but not in parietal-temporal cortex or in hypothalamus (CRF concentrations in the hippocampus were not detectable): CRF content in the prefrontal cortex was higher in BN than in the other strains, although the differences with FIS were not statistically significant; in the pons-medulla, FIS and LEW showed significantly higher CRF content than the other strains. From the present results it appears that BN and WKY rats were more prone to adopt passive strategies in the FST, but they did not show higher brain CRF immunoreactivity or down-regulation of CRF receptors. Hence, although there were inter-strains differences in all variables studied, no evidence for a relationship between the FST behaviour and central CRF activity was found.

Animals↗

PubMed1997

Inhibition of corticosteroid-binding globulin caused by a severe stressor is apparently mediated by the adrenal but not by glucocorticoid receptors.

The effect of stress on serum corticosteroid-binding globulin (CBG) was studied in adult male Sprague-Dawley rats. CBG was measured either by a homologous radioimmunoassay (RIA) or by a binding assay (BA) using 3H-corticosterone. Exposure of adult male rats to a severe stressor such as immobilization (IMO) for 1 h did not alter serum CBG levels, but a significant decrease was found after 6 and especially 24 h IMO. This decrease was not observed after 24 h exposure to a milder treatment such as food and water deprivation. The effect of different periods of exposure to two stressors, IMO or restraint, was also studied. The following results were obtained:serum CBG levels were reduced by IMO, but only by restraint; IMO-induced reduction of CBG levels was always observed 24 h after starting exposure to IMO, independently of the actual period of exposure to the stressor; and IMO-induced inhibition of CBG was proportional to the hours of exposure to the stressor. Although IMO-induced inhibition of CBG was prevented by adrenalectomy, a role for glucocorticoid acting through their classical type II receptors is unclear as far as treatment of rats with the glucocorticoid receptor antagonist RU486 (100 mg/kg) did not prevent the inhibition caused by IMO. The present data clearly indicate that acute exposure to a stressor is able to decrease CBG levels provided that duration of exposure to the stressor and its intensity are high and that the effect is tested at least 6 h after the onset of stress. The effect appears to be mediated by some adrenal factor(s) other than glucocorticoids.

Adrenal Glands↗

PubMed1997

Chronic immobilization stress reduces sodium intake and renal excretion in rats.

The influence of chronic exposure to immobilization (IMO) on sodium appetite as well as sodium and potassium renal excretion in adult male Wistar rats was studied. The animals were individually housed and all variables under observation were measured in metabolic cages the first, seventh, and thirteenth days once the experiment had started. Half of the rats had access to water, and the remainder of the rats had access to both water and saline solution (1.5% NaCl). IMO reduced the intake of saline solution. Renal water, sodium, and potassium excretion in those IMO rats having access to saline were lower than in control rats. The effects of IMO were very similar during all observation days; therefore no evidence of adaptation to repeated stress was found. The present data indicate the following: (i) IMO stress reduced sodium appetite, probably as a secondary effect to the deficit in sodium renal excretion; (ii) IMO caused antidiuresis and antikaliuresis, only in those rats taking saline solution; (iii) no adaptation to repeated IMO stress was found in any of the tested variables. The reduction of sodium appetite observed in stressed rats might be a homeostatic mechanism to maintain sodium balance after impairment of renal sodium excretion caused by stress.

Animals↗

PubMed1997

Influence of Regularity of Exposure to Chronic Stress on the Pattern of Habituation of Pituitary-Adrenal Hormones, Prolactin and Glucose.

The effect of regularity of exposure to two different chronic stressors (noise or immobilization (IMO)) on the pattern of habituation of pituitary-adrenal (PA) hormones, prolactin and glucose was evaluated in adult male rats. Animals were chronically subjected to either regular or irregular time schedule of noise (30 min/day) or IMO (2 h/day) for two weeks. The day after the last stress session the rats were killed without stress or after having been subjected to 30 min of the homotypic stressor. Whereas regular noise did not affect food intake, body weight gain or adrenal weight, irregular noise decreased body weight gain and induced a moderate adrenal hypertrophy. In addition, previous daily exposure to regular but not to irregular noise reduced both prolactin and corticosterone responses to acute noise. In contrast, glucose response to acute noise was reduced after both regular and irregular exposure to chronic noise. Either regular or irregular exposure to chronic IMO decreased food intake and body weight and increased adrenal weight to the same extent. Likewise, no influence of regularity of exposure to chronic IMO on corticosterone and prolactin responses to acute IMO was observed. However, habituation of the ACTH response to acute IMO was observed in rats subjected to chronic regular IMO, but not in rats subjected to chronic irregular IMO. Finally, acute IMO-induced hyperglycemia diminished to the same extent after regular and irregular IMO. From these results we can conclude that: first, the process of habituation of the PA axis to chronic stress is greatly dependent upon factors such as regularity of exposure to the stressor and stressor intensity, and second, the influence of regularity on the pattern of habituation to a repeated stressor is dependent on the physiological variable we are dealing with.

Journal Article↗

PubMed1996

Differential responsiveness of inbred strains of rats to antidepressants in the forced swimming test: are Wistar Kyoto rats an animal model of subsensitivity to antidepressants?

In three experiments we have studied the effects of acute administration of various doses (5, 10, 15 and 25 mg/kg) of desipramine (DMI) and two doses (0.5 and 2 mg/kg) of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5HT1A receptor agonist, on behaviour of five inbred strains of rats in the holeboard and the forced swimming test (FST). The strains were Brown-Norway (BN), Fischer 344 (FIS), Lewis (LEW), Spontaneously Hypertensive Rats (SHR) and Wistar-Kyoto (WKY). In drug-free conditions, the strains showed striking differences in their activity in the holeboard and in the FST, the WKY rats being the most passive in both tests. The dose of 15 mg/kg DMI caused a profound inhibitory effect on locomotor/exploration activity in all strains. In the FST, this dose of DMI increased struggling and reduced immobility in BN, FIS and LEW rats, but did not exert any effect in SHR and WKY rats. The lack of marked strain-dependent differences in the sensitivity to the inhibitory effects of DMI on locomotor activity or exploration rule out a major role of changes in the metabolism of drug among strains as an explanation for differential response to DMI in the FST. In further experiments three strains were used: BN (responsive), WKY (non-responsive) and the outbred Sprague Dawley (SD) rats. In the FST, both DMI and 8-OH-DPAT, at all doses, decreased immobility and increased struggling in BN and SD rats. However, WKY rats responded only to a very high dose of DMI (25 mg/kg). Hence, WKY rats are not only passive in the FST, but are also subsensitive to acute antidepressant administration. The present data indicate that the levels of activity of animals in the FST in drug-free conditions are not predictive of their response to antidepressants, and that inbred strains might be useful for studying the biological basis of subsensitivity to antidepressants and depressive-like behaviour.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1996

Fawn-hooded rats show enhanced active behaviour in the forced swimming test, with no evidence for pituitary-adrenal axis hyperactivity.

Fawn-hooded (FH) rats have been reported to have high basal corticosterone levels that can be normalized by antidepressant administration. In the present work, some behavioural and endocrine aspects were compared in FH and Sprague-Dawley (SD) rats. No interstrain differences in basal corticosterone levels or response to acute tail-cut stress were observed either in the morning or in the evening. Relative adrenal weight was lower in FH than SD, and relative thymus weight was, accordingly, higher in FH than SD rats. FH rats were hyperactive in the holeboard and showed behaviour similar to that of SD in the plus-maze. In contrast, FH rats showed greater levels of active behaviour (struggling) and lower levels of immobility than SD rats in the forced swimming test (FST). After desipramine (DMI) administration the differences between the two strains in the FST were more marked than in vehicle-treated animals. These results indicate that FH rats show no signs of pituitary-adrenal (PA) hyperactivity or depression-like behaviour, and therefore they are not an appropriate animal model of depression.

Adrenal Glands↗

PubMed1996

Forced swimming behavior is not related to the corticosterone levels achieved in the test: a study with four inbred rat strains.

The behavior of four inbred strains of rats in the holeboard and the forced swimming tests, and its relationship with a physiological index of stress (serum corticosterone) were studied in adult male rats. The strains were: Fisher 344 (FIS), Lewis (LEW), Spontaneously hypertensive (SHR), and Wistar-Kyoto (WKY). In the holeboard, SHR rats were the most active and WKY the less active, the other strains showing intermediate levels of activity. During the first exposure to forced swimming WKY were far more passive than the other three strains and the same was observed during the second exposure. When corticosterone levels after this second exposure to water was determined, LEW rats showed lower values than the other three strains. Therefore, no apparent relationship between behavior and stress-induced corticosterone secretion exists. Although a single point measurement of only on physiological index of stress has important limitations, the present data do not give support to a strong relationship between the behavior of the animals in the forced swimming test and emotional reactivity to stress. It is therefore possible that forced swimming behavior might not be mainly a panic-like reaction, but the result of the tendency of the animals to adopt passive strategies in inescapable situations. Although more studies are needed to firmly establish this assumption, WKY rats might be, at least potentially, a useful model of depressive-like behavior.

Animals↗

PubMed1996

The effects of two chronic intermittent stressors on brain monoamines.

The effects of chronic exposure (27 days) to two different stressors on brain monoaminergic activity was studied in adult male rats. The stressors used were restraint in tubes (RES) and immobilization in wooden boards (IMO). Both chronically stressed and stress naive (control) rats were subjected to 0, 15, and 60 min of the same stressor to which they were chronically exposed. Previous chronic exposure to either RES or IMO significantly reduced ACTH response to the same stressor. Monoaminergic response to these stressors was studied by measuring the levels of noradrenaline (NA), serotonin (5-HT) and their metabolites: 3-methoxy,4-hydroxyphenyletileneglycol sulfate (MHPG-SO4) and 5-hydroxyindoleacetic acid (5-HIAA), respectively. The regions studied were: pons plus medulla, midbrain, hypothalamus, hippocampus, and frontal cortex. Previous chronic exposure to the stressors induced only few changes in the resting levels of the monoamines and their metabolites. In addition, monoaminergic response to the same stressor to which they were chronically exposed was always similar in control and chronically stressed rats. These data indicate that brain NA and 5-HT metabolism is less sensitive than ACTH to the process of habituation to a repeated stressor, at least in the gross areas of the brain analyzed in the present study.

Adrenocorticotropic Hormone↗

PubMed1996

Acute stress markers in humans: response of plasma glucose, cortisol and prolactin to two examinations differing in the anxiety they provoke.

Although the endocrine response to psychological stressors has been extensively studied both in animals and humans, the sensitivity of these variables to the intensity of stress experienced by exposure to psychologically stressful situations has not been studied in humans. In the present work this was assessed by measuring plasma levels of glucose, cortisol and prolactin in female medical students just before taking two examinations clearly differing in the anxiety they provoke. It was found that both examinations increased anxiety just before taking them, but the physiology examination (EPh) caused higher anxiety than the psychology (EPs). Prolactin increased in response to both examinations as compared to the non-stress condition, but its levels were greater in the EPh than in the EPs. Cortisol followed the same pattern as prolactin, but increased only marginally in the EPs. Finally, glycemia rose to the same extent in response to both examinations. A significant positive correlation was found between anxiety and glucose, and between cortisol and prolactin when data from all situations were included. On the basis of these results, it appears that the three variables might be useful as putative markers of stress in humans, although glucose might reflect different underlying psychological processes than cortisol and prolactin. In addition, it was found for the first time that prolactin is able to discriminate between stressful situations of different intensity. The response of these physiological variables to other stressful situations differing both in quantitative and in qualitative terms merits to be studied in further work.

Adult↗

PubMed1996

Hypothalamic-pituitary-adrenal response to chronic stress in five inbred rat strains: differential responses are mainly located at the adrenocortical level.

The effects of chronic stress on the hypothalamic-pituaitary-adrenocortical (HPA) axis were studied in five inbred rat strains, i.e. Brown Norway (BN), Fischer (FIS), Lewis (LEW), Spontaneously Hypertensive (SHR) and Wistar Kyoto (WKY). Previously, these rat strains had been shown to display clear behavioral differences in the forced swimming test that presumably measures depression-like behavior, BN and WKY being more passive than the other strains. Here we test the hypothesis that the differences in behavioral immobility might be associated with an abnormal HPA response to chronic immobilization (IMO) stress. In stressnaive rats under basal conditions (morning) there were no differences among strains in adrenal weight, serum adrenocorticotropin hormone (ACTH) and corticosterone (B) levels, cortictropin-releasing factor (CRF) mRNA in the hypothalamic paraventricular nucleus (PVN) and hippocampal glucocorticoid and mineralocorticoid receptor (GR and MR) mRNA. After chronic IMO, basal serum ACTH levels were increased in LEW, SHR and WKY, but not in BN or FIS rats, whereas basal B levels were increased in BN, FIS, SHR and WKY rats, but not in LEW. The increase in adrenal weight was also strain dependent and correlated negatively with chronic IMO-induced hypercorticosteronemia. These peripheral differences among strains were not observed at central levels. Thus, chronic IMO increased the CRF mRNA content in the PVN, analyzed by in situ hybridization, similarly in all strains. In addition, after chronic IMO no differences were found among strains in hippocampal GR mRNA and RM mRNA contents. Considering data from all strains together, chronic IMO reduced the GR mRNA (50-60%) content in the hippocampal CA1, CA3 and DG areas, and slightly diminished (11-13%) MR mRNA levels in CA1 and CA3 areas. The present results indicate that: (i) chronic IMO down-regulates GR mRNA in the hippocampus and slightly up-regulates CRF mRNA in the hypothalamic PVN similarly in all strains; (ii) after chronic IMO interstrain differences were observed in serum ACTH and B levels as well as adrenal hypertrophy; (iii) some changes are probably located at the adrenal level since changes in serum B level and adrenal weight were not related to changes in ACTH; (iv) in LEW and WKY rats, B hyporesponsiveness to chronic IMO might be linked to low adrenal sensitivity to ACTH, and (v) HPA axis changes induced by the chronic IMO procedure are not related to previously reported data on depressive-like behavior of BN and WKY in the forced swimming test.

Adrenal Cortex↗

PubMed1996

Acute stress attenuates but does not abolish circadian rhythmicity of serum thyrotrophin and growth hormone in the rat.

The effects of acute immobilization (IMO) on daily rhythms of corticosterone, thyroid-stimulating hormone (TSH) and growth hormone (GH) were studied in adult male rats. Two hours of IMO increased serum corticosterone, this increase still being observed 3 h after finishing stress exposure. In the dark period corticosterone levels did not differ in control and IMO rats, but higher levels were observed again in the morning of the day after. Immobilization lowered serum GH and TSH levels throughout the 24-h period that followed exposure to the stressor. Such an effect was more marked in GH than in TSH. In addition, GH, but not TSH, levels were found to be reduced significantly by IMO at 08.30 h of the next day. None the less, daily rhythms of GH and TSH were still persistent and roughly similar to those of control rats. The daily rhythm of food intake was measured in a separate experiment and it was observed, as expected, that IMO reduced food intake only in the dark period of the lighting cycle. It appears therefore unlikely that IMO-induced anorexia was the major factor responsible for the inhibition of GH and TSH caused by IMO at 11.00 and 19.00 h, considering that the amount of food intake was very low and similar in control and IMO rats during this period. However, anorexia might have contributed to inhibition of GH and TSH secretion afterwards. Thus, in a third experiment we studied the contribution of IMO-induced anorexia to the changes in hormone levels observed 24 h after stress by introducing a group of pair-fed rats. It was found that IMO, but not pair-feeding, reduced TSH levels, whereas a similar reduction of GH was found in the two conditions. It might be concluded that acute stress transiently altered corticosterone secretion, the only long-lasting effect being a slight increase in its morning levels on the following stress. Immobilization also causes an inhibition of GH and TSH secretion in the rat that persists for several hours after finalization of exposure to the stressor, but daily rhythms were still apparent. It appears that the contribution of stress-induced anorexia is different in GH than in TSH. In conclusion, an acute severe stressor such as IMO, although modifying circulating levels of some hormones, particularly in the hours following exposure to the stressor, did not appear to interfere greatly with the expression of circadian rhythms of anterior pituitary hormones.

Acute Disease↗