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C Guaza

Publications and source records attributed to C Guaza.

At least 37 records · Page 2Linked to original sources
PubMed1996

Novelty-related rapid locomotor effects of corticosterone in rats.

Glucocorticoids modulate brain function and behaviour through different mechanisms. Although classical effects are mediated through intracellular receptors that modulate gene transcription, recent evidence supports the existence of rapid, nongenomic steroid effects through the neuronal membrane. In this study, we explored possible rapid behavioural effects of corticosterone in the rat, which could provide a model to characterize further the mechanisms involved in rapid corticosteroid nongenomic actions. We found that a corticosterone injection, at doses (2.5 or 5 mg/kg) that mimic plasma concentrations produced by substantial stress, rapidly increases (within 7.5 min of its systemic administration) the locomotor response displayed by rats in a novel environment (activity cage). A lower dose of 1 mg/kg failed to induce this effect. In addition, corticosterone failed to increase locomotion when administered to rats that had been previously exposed to the activity cage. Corticosterone-induced increased locomotion in a novelty situation was not counteracted by either the intracerebroventricular administration of the protein synthesis inhibitor cycloheximide, or by the intracerebroventricular administration of specific antagonists for each type of intracellular corticosteroid receptor, i.e. RU28318, a mineralocorticoid receptor antagonist and RU38486, a glucocorticoid receptor antagonist. Further studies supported the viability of the receptor antagonists to display an anti-corticosteroid action interfering, as previously reported, with the behavioural &winning test. Therefore, the rapid actions of corticosterone in locomotor activity described here, which appear to be nongenomic, might provide a model for future research on the elucidation of the mechanisms involved in steroid-membrane interactions.

Animals↗
PubMed1996

Nitric oxide synthesis inhibitors prevent rapid behavioral effects of corticosterone in rats.

Corticosteroid actions at the brain can modulate neural function and behavioral processes. Classic corticosteroid effects are mediated through intracellular receptors which act primarily by regulation of DNA transcription. However, an alternative nongenomic mechanism mediating rapid corticosteroid actions by effecting the neuronal membrane has also been proposed. We have recently described a behavioral model of rapid corticosterone effects fulfilling criteria for considering nongenomic steroid actions, such as resistance to protein synthesis inhibition and to blockage of intracellular receptors through the use of specific receptor antagonists. The model consists of a rapid increase induced by a corticosterone injection (within 7.5 min of a systemic injection) on the locomotor response displayed by rats in a novel environment. In the present study, we aimed to study whether the gas molecule nitric oxide might be included among the effector systems involved in such rapid corticosterone effect. The administration of nitric oxide synthase inhibitors, given either systemically [NG-nitro-L-arginine methyl ester (L-NAME), 30 mg/kg body weight, i.p.] or centrally [N-nitro-L-arginine (N-Arg), 10 microliters of a 10-mM solution i.c.v.], prevented the increase in locomotion induced by corticosterone (Cort, 5 mg/kg body weight i.p.). Specificity of this effect was supported by the ability of the nitric oxide precursor L-arginine (L-Arg, 350 mg/kg body weight i.p.) to inhibit L-NAME action. This effect of nitric oxide synthase inhibition on steroid effects was shown to be task-specific, since L-NAME failed to influence another rapid behavioral effect of corticosterone, the suppression of the acoustic startle response. Under our experimental conditions, corticosterone failed to affect peripheral blood pressure, discarding that the antagonistic effect of nitric oxide synthase inhibition on the corticosterone-induced effect in locomotion were related to a peripheral action at the cardiovascular level. Therefore, these data suggest a role for nitric oxide on the neurochemical mechanisms elicited by corticosterone to rapidly enhance locomotion in a novel situation.

Acoustic Stimulation↗
PubMed1995

Decreased spontaneous motor activity and startle response in nitric oxide synthase inhibitor-treated rats.

In the central nervous system, nitric oxide has been proposed to be a retrograde messenger mediating learning and synaptic plasticity. Since only pretraining injections of nitric oxide synthesis inhibitors were shown to impair learning, we examined the possibility that systemic administration of these inhibitors might influence some non-specific aspects related to the organism's general psychophysiological status. Intraperitoneal administration of NG-nitro-L-arginine methyl ester (30 or 100 mg/kg) 60 min pre-test to adult rats resulted in: (i) altered exploratory pattern and reduced locomotion in a novel environment; (ii) reduced startle response to either acoustic or electric stimuli; and (iii) cardiovascular alterations. In addition, intracerebroventricular administration of N-nitro-L-arginine (10 microliters of a 10 mM solution) diminished the acoustic startle response. Specificity of these effects through nitric oxide was supported by the ability of the nitric oxide precursor, L-arginine, to prevent the inhibitors actions. These findings indicate that nitric oxide inhibitors interfere with the general psychophysiological status of the organism.

Acoustic Stimulation↗
PubMed1995

Evidence for a role of nitric oxide in the corticotropin-releasing factor release induced by interleukin-1 beta.

Interleukin-1 beta stimulates corticotropin-releasing factor (CRF) secretion from the hypothalamus involving the activation of prostaglandins. This study investigated the possibility that nitric oxide (NO) acts as a mediator of interleukin-1-induced CRF release. An in vitro rat hypothalami continuous perifusion system was used. Pre- and co-incubation of hypothalami with either the NO synthase inhibitor, NG-nitro-L-arginine (1 mM), or the NO scavenger, hemoglobin (10 microM), induced a marked reduction in the effect of interleukin-1 (3 pM) on CRF secretion. The effect of NG-nitro-L-arginine was prevented by pre-exposure of hypothalami to L-arginine (1 mM). We also studied whether the involvement of NO in this interleukin-1 effect could involve a prostaglandin action. The concurrent treatment with NG-nitro-L-arginine and indomethacin (14 microM)--an inhibitor of prostaglandin production--reduced interleukin-1-induced CRF release to the same level as NG-nitro-L-arginine alone, suggesting that prostaglandins might interact with NO on this interleukin-1 effect. These results suggest that NO plays a role in the in vitro stimulatory action of interleukin-1 on hypothalamic CRF secretion.

Analysis of Variance↗
PubMed1995

Evidence for cyclooxygenase activation by nitric oxide in astrocytes.

We have evaluated the role of nitric oxide (NO) on the cyclooxygenase pathway in mouse glial cells. Exposure of primary cultures of neonatal mouse cortical astrocytes to bacterial lipopolysaccharide (LPS; 1 microgram/ml, 18 h) caused an increase in the release of both nitrite (NO2-) and prostaglandin E2 (PGE2), products of NO synthase (NOS) and cyclooxygenase, respectively. Production of both, NO2- and PGE2 by astrocytes, was inhibited by the exposure of the NOS inhibitor Nw-nitro-L-arginine methyl ester (L-NAME: 1, 10, and 100 microM) in a dose related manner. Besides, other NOS inhibitors such as Nitro L-arginine (NNA: 10(-3) M) prevented the increase in PGE2 release from LPS-stimulated astrocytes. Sodium nitroprusside (SNP; 100-200 microM) used as a NO donor caused a dose-related enhancement in the accumulation of PGE2 induced by LPS and the presence of hemoglobin blocked the SNP effects. The exposure to SNP counteracted the decrease of PGE2 production in LPS-treated astrocytes in which NO synthesis was blocked by L-NAME. In addition, SNP also enhanced the synthesis of PGE2 following exogenous arachidonic acid astrocytes exposure. Interestingly, this effect was blocked by indomethacin. Treatment of astrocytes cultures with dexamethasone (0.1, 1 microM) blocked dose-relatedly the LPS-induced release of both NO2- and PGE2. As expected, the presence of indomethacin (1, 10, and 20 microM) prevented in a dose related fashion, PGE2 production by astrocytes following exposure to LPS. These results strongly indicate that in astroglial cells, NO is able to activate the cyclooxygenase pathway.

Animals↗
PubMed1995

Cytokine regulation of corticosteroid receptors in the rat hippocampus: effects of interleukin-1, interleukin-6, tumor necrosis factor and lipopolysaccharide.

The effects of interleukin-1 beta (IL-1), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF) and lipopolysaccharide (LPS) on hippocampal corticosteroid receptors were studied in the rat. Type I (mineralocorticoid) and type II (glucocorticoid) receptors were measured in hippocampal cytosolic fractions with the radioligand binding technique, using 3H-corticosterone and 3H-RU 28362, respectively. LPS, administered intraperitoneally (50 micrograms/kg 8 h before sacrifice or 100 micrograms/kg injected twice, 16 and 8 h before sacrifice) to rats which had been previously adrenalectomized to allow for clearance of endogenous corticosterone, did not modify either type of corticosteroid receptors in the hippocampus. IL-1, IL-6, TNF or saline were injected intracerebroventricularly (50 ng/rat) and the animals were killed 3 h after. Type I receptors were not affected by any of the cytokines studied. Moreover, no changes in type II receptors were observed after IL-1 or IL-6 administration. In contrast, hippocampal type II receptors were dramatically decreased after the injection of TNF. The TNF-induced downregulation of type II receptors was secondary to a marked decrease in the affinity of the receptors (Kd increased 7.2-fold), accompanied by a 51% decrease in receptor number (Bmax). These results emphasize the important role played by TNF in the modulation of the hypothalamic-pituitary-adrenal axis during immune/inflammatory processes and extend the central sites of action of this cytokine to the corticosteroid receptors of the hippocampus.

Animals↗
PubMed1994

Corticosteroid regulation of IL-1 receptors in the mouse hippocampus: effects of glucocorticoid treatment, stress, and adrenalectomy.

Interleukin-1 (IL-1) and glucocorticoid hormones represent two key mediators involved in the modulation of the neuroimmunoendocrine response to stress. IL-1 is a potent activator of the hypothalamic-pituitary-adrenal (HPA) axis in rodents. In the immune system, glucocorticoids modulate IL-1 production and a number of IL-1 receptors. However, little information is currently available about the modulatory effects that glucocorticoids might exert on IL-1 receptors in the central nervous system. To this purpose, we carried out a series of studies to investigate the effects of various manipulations of the HPA axis on IL-1 binding to the murine hippocampus. Our results show that IL-1 receptor levels in the hippocampus were slightly decreased below control values in dexamethasone (DEX)-treated animals (0.25 or 1 mg/kg i.p. every 12 h) either in subchronic (5 doses) or chronic (8 days) treatments. Corticosterone (CORT) resulted in a small reduction in IL-1 receptors only when injected subchronically at the dose of 5 mg/kg. When it was given at a lower dose (1.25 mg/kg), injected chronically or implanted subcutaneously as CORT pellets for 8 days, no effect was observed. Neither glucocorticoid modified IL-1 binding when administered as a single injection. Saturation studies after subchronic corticosteroid treatment did not reveal modifications in the number and/or affinity of IL-1 receptors in the hippocampus. The regulation of IL-1 receptors by glucocorticoids was also studied following stimulation of IL-1 production by lipopolysaccharide (LPS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed1992

Adrenalectomy does not change CRF secretion induced by interleukin-1 from rat perifused hypothalami.

Interleukin-1 (IL-1) is a potent hypothalamic-pituitary-adrenal (H-P-A) axis activator. The hypothalamus is considered one of the main sites of action of IL-1 on the H-P-A axis, inducing CRF secretion, which is modulated by glucocorticoids. Glucocorticoids, which modulate CRF release by a negative feedback inhibition, have been postulated to exert a permissive action on the IL-1 effect on CRF secretion. Using a continuous perifusion system of rat hypothalami, the results of the present study indicate that at the same concentrations, IL-1 beta exerted a more potent effect than IL-1 alpha stimulating CRF secretion. The increase in hypothalamic CRF release induced by IL-1 was rapidly inhibited by both dexamethasone and corticosterone. However, adrenalectomy 2 or 8 days before did not modify CRF secretion induced by IL-1 from the in vitro perifused hypothalami. These data indicate that IL-1 does not seem to induce CRF secretion by interfering with an impeding action of glucocorticoids, although the cytokine effect is negatively modulated by corticosteroids.

Adrenalectomy↗
PubMed1992

Activity of the hypothalamic-pituitary-adrenal axis in mice selected for left- or right-handedness.

Asymmetry in brain modulation of the immune system has been previously described. In mice, paw preference has been shown to be associated with immune reactivity but the mechanisms involved in such an association are not yet known. The autonomic nervous system and the neuroendocrine system are considered as major candidates for neural influences on the immune system. In the present study, the activity of the hypothalamic-pituitary-adrenal (HPA) axis of adult female mice selected for paw preference (left-handers vs. right-handers) was assessed by measuring both adrenocorticotropic hormone (ACTH) and corticosterone plasma levels, as well as the in vitro responses of hypothalamus and adrenocortical cells to various hormone releasing stimuli. The results reported here showed no difference in the activity of the HPA axis between left- and right-handed mice, suggesting that this neuroendocrine axis is not implicated in the association between functional brain asymmetry and immune reactivity. However, our results do not exclude the possibility that the HPA axis could play a role in such an association under other circumstances, such as during development or stressful situations.

Adrenocorticotropic Hormone↗
PubMed1992

Release of corticotropin-releasing factor from superfused rat hypothalami induced by interleukin-1 is not dependent on adrenergic mechanism.

Interleukin-1 (IL-1) is a potent activator of the hypothalamic-pituitary-adrenal (HPA) axis. The hypothalamus seems to be the most important site of action of IL-1 on the HPA axis, inducing corticotropin-releasing factor (CRF) secretion. Catecholamines are important modulators of CRF secretion. In turn, IL-1 stimulates catecholamine release from the hypothalamus. In the present study, we examined the possible involvement of hypothalamic catecholamines in the effect of IL-1 beta on hypothalamic CRF secretion, by using an in vitro rat hypothalami continuous perifusion system. Neither in vivo pretreatment with an inhibitor of catecholamine synthesis nor in vitro exposure to alpha- or beta-adrenoceptor antagonists (phenoxybenzamine or propranolol, respectively) nor combination of both treatments altered the effect of IL-1 on CRF secretion from superfused hypothalami. These data indicate that catecholamines are not involved in the in vitro stimulatory action of IL-1 on hypothalamic CRF secretion.

Adrenocorticotropic Hormone↗
PubMed1992

Behavioral factors in stress-induced immunomodulation.

Individual differences in the exploratory response to novelty were found to be related with the vulnerability to develop stress-induced immunological alterations. We studied the effect of exposure to inescapable shock on antibody formation against sheep red blood cells (SRBC) in rats selected according to their locomotor activity in a novel situation. Interestingly, antibody titers were only enhanced in shocked animals with the highest locomotor activity. These results emphasize the importance of taking into account individual differences for the study of the mechanisms involved in stress-induced immunomodulation, suggesting a behavioral procedure (novelty reactions) to deal with individual variability in the effects of stress on the immune system.

Animals↗
PubMed1992

Behavioral, neuroendocrine, and immunological outcomes of escapable or inescapable shocks.

The present study was designed to evaluate the effects of repeated exposure to escapable or inescapable shocks on subsequent behavior in an activity cage, and on the reactivity of the hypothalamic-pituitary-adrenocortical (HPA) axis and the immune system. We also studied the possible influence of behavioral factors on the behavioral and physiological impact of stress. Although exposure to different stressful situations pointed out marked differential effects in subsequent behavior, it failed to elicit differences in the neuroendocrine and immunological parameters studied. However, interesting results were found in analyzing the influence of behavioral factors. The degree of control exerted over the shock was inversely related to ACTH and corticosterone levels. In addition, individual differences in the exploratory activity to novelty were correlated with poststress lymphoproliferation and antibody formation. These data indicate that the behavioral and physiological outcomes of stress depend on the interrelations between environmental and individual factors (including both preexisting individual differences and the coping responses during stress).

Adrenocorticotropic Hormone↗
PubMed1992

Role of arachidonic acid metabolism on corticotropin-releasing factor (CRF)-release induced by interleukin-1 from superfused rat hypothalami.

The present work shows that the corticotropin-releasing factor (CRF)-releasing activity of interleukin-1 (IL-1) is partially inhibited by a phospholipase A2 (mepacrine) or a cyclooxygenase (indomethacin) inhibitor, but is not affected by inhibition of the lypoxygenase pathway with norhydroguaiaretic acid. These results indicate that the metabolism of arachidonic acid plays an important role as mediator of the effects of IL-1 on CRF release. It is also shown that products of the cyclooxygenase activity such as prostaglandins can stimulate CRF secretion by a direct action on the hypothalamus. Whereas PGE2 failed to induce increases on CRF release, PGF2 alpha stimulated in a dose-dependent manner (21-340 nM), the CRF release from continuous perifused hypothalami. It is suggested that PGF2 alpha could be involved as a messenger in the hypothalamic CRF secretion induced by IL-1.

Animals↗
PubMed1992

Effects of HPA hormones on adapted lymphocyte responsiveness to repeated stress.

Acute stress-induced immune alterations can result in adapted function with prolonged exposure to the same stressor. The present study was designed to evaluate the possible role of the hypothalamic-pituitary-adrenocortical (HPA) axis on the adaptation of spleen lymphocyte responsiveness to repeated stress. For this purpose, we selected a stressful protocol (aversive auditory stimulation) that induced an initial suppression (1 day), followed by a return to control values with repeated application (4 days), of mitogen-induced lymphocyte proliferation. Because rats exposed to 4 days of noise sessions show enhanced adrenocorticotropin (ACTH) and corticosterone levels, we tested the possibility that adaptation of lymphoproliferation by repeated stress was due to a desensitization of splenic lymphocytes to stress-released HPA hormones. The results showed that corticotropin-releasing factor (10(-9) M) and corticosterone (5 x 10(-8) and 10(-7) M), as well as dexamethasone (10(-8), 5 x 10(-8), and 10(-7) M), significantly suppressed lymphoproliferation from both control and stressed rats in a similar way. ACTH (10(-9) and 5 x 10(-9) M) did not significantly influence Concanavalin-A-stimulated spleen lymphocytes. These data indicate that adaptation of lymphocyte proliferation by repeated noise stress occurs without accompanying alterations in lymphocyte responsiveness to HPA hormones.

Acoustic Stimulation↗
PubMed1992

Interleukin-1-beta induces pituitary adrenocorticotropin secretion: evidence for glucocorticoid modulation.

Using an in vitro continuous perifusion system, the effects of interleukin-1 (IL-1) on adrenocorticotropin (ACTH) secretion at the pituitary level were investigated. On one hand, we observed that IL-1 beta increases ACTH secretion from perifused anterior pituitary cells in a dose-dependent manner, between 1.5 and 6 pM. This stimulatory action of IL-1 on ACTH was significantly attenuated by a short in vitro dexamethasone pretreatment. This fact suggests a regulatory glucocorticoid negative feedback analogous to that observed upon the pituitary action of corticotropin-releasing factor (CRF). We also examined the effect of simultaneous treatment with IL-1 and CRF. The results indicated that the effect of IL-1 resulted additive to the CRF-induced ACTH secretion. It is concluded that the anterior pituitary could be an important site of IL-1 action to activate the hypothalamic-pituitary-adrenocortical axis function, and that this action is under an inhibitory glucocorticoid regulation.

Adrenocorticotropic Hormone↗
PubMed1992

Mutually antagonistic effects of corticosterone and prolactin on rat lymphocyte proliferation.

The present study was designed to evaluate the immunological outcome resulting from experimental conditions involving different corticosterone and prolactin ratios in rats. One set of experiments was conducted to assess the effects of prolactin and corticosterone on the in vitro mitogen-induced proliferation of spleen lymphocytes from animals previously submitted to the manipulation of their glucocorticoid status throughout adrenalectomy (ADX) and/or exposure to acute stress. The results indicated that prolactin (5 x 10(-9) M) induced a significant increase in concanavalin A- (ConA) induced proliferation of splenocytes only from ADX-control, unstressed, rats. However, a lower dose of prolactin (10(-9) M) failed to influence lymphoproliferation. Corticosterone (2 x 10(-8) and 10(-7) M) induced a dose-dependent reduction in lymphocyte proliferation in all experimental groups. Further experiments were conducted to study the relative potency of prolactin to antagonize the in vitro corticosterone-induced suppression of ConA-stimulated lymphocytes. The results showed, on the one hand, that higher doses of prolactin (10(-8) and 5 x 10(-8) M) were effective in stimulating ConA-induced lymphocyte proliferation in control, undisturbed, rats. They also showed that when prolactin and corticosterone are simultaneously added to the cultures, the immunostimulatory effect induced by a dose of 10(-8) M of prolactin can either predominate over a weak suppressive action of corticosterone (2 x 10(-8) M) or totally antagonize to normal values a marked immunosuppression induced by a higher dose of corticosterone (10(-7) M). These data support the view that different ratios between prolactin and corticosterone concentrations can result in differential immunological outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗