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J Borrell

Publications and source records attributed to J Borrell.

At least 19 recordsLinked to original sources
PubMed1998

Effect of endotoxin and interleukin-1beta on corticotropin-releasing-factor and prostaglandin release by rat brainstem slices.

This study investigated the effects of lipopolysaccharide (LPS) and interleukin-1beta (IL-1beta) on corticotropin releasing factor (CRF) and prostaglandin E2 (PGE2) release by brainstem slices in vitro. First, we characterized our experimental model and demonstrated that high potassium stimulates CRF release from rat brainstem slices in a calcium dependent way. The direct stimulation of brainstem slices with IL-1beta (3-25 pM) did not modify basal or potassium-stimulated CRF release, although IL-1beta at the dose of 25 pM increased PGE2 production. Peripheral injection (i.p.) of LPS (1-10 microg/kg) or IL-1beta (1-10 microg/kg) evoked a dose-related potentiation of the ex-vivo release of CRF and PGE2 from brainstem slices. However, central (i.c.v.) administration of LPS (10-500 ng/rat) potentiated the release of CRF and PGE2 only at the dose of 500 ng/rat, whereas IL-1beta (1-100 ng/rat) failed to modify significantly the ex vivo production of both CRF and PGE2. The results of the present study provide evidence that peripheral, rather than central, endotoxin and IL-1beta administration induce the activation of brainstem CRF and PGE2, supporting the hypothesis that peripheral cytokine signalling to the CNS is mediated by stimulation of peripheral afferents.

Animals↗
PubMed1995

Contribution of NMDA and nonNMDA glutamate receptors to synchronized excitation and cortical output in the primary motor cortex of the rat.

Application of a GABA (gamma-aminobutyric acid) type A receptor antagonist through a microdialysis probe into the forelimb primary motor cortex (MI) of ketamine anesthetized rats induced the appearance of paroxysmal field potentials recorded in the supragranular layers of the MI and concomitant electromyographic (EMG) activity in the contralateral forelimb. Application of a nonNMDA (N-methyl-D-aspartate) glutamate receptor antagonist in conjunction with the GABA type A receptor antagonist completely blocked the paroxysmal field potentials and the EMG activity of the contralateral forelimb, while a NMDA receptor antagonist had no effect. The results indicate that the spread of activity within the primary motor cortex and the motor cortex output are mediated by nonNMDA receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
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

Scopolamine induces recovery of shuttle box avoidance behavior after frontal cortex ablation.

The learning and reversal of shuttle box active avoidance behavior in animals with a bilateral frontal cortex ablation was investigated during and after scopolamine or pilocarpine treatment. Scopolamine facilitated the performance of the avoidance task in normal animals and in those with frontal cortex lesions and also increased the number of intertrial responses, while pilocarpine increased the deleterious effects of the lesions. Furthermore, in the absence of scopolamine, the animals previously treated with the drug showed that its beneficial effects persisted while the number of intertrial responses were no longer increased. The results indicate that the beneficial effects of scopolamine treatment on active avoidance behavior are independent from the effects observed on intertrial activity since only the former are observed after drug withdrawal. Therefore, scopolamine treatment seems to induce a long lasting recovery process in frontal cortex ablated animals.

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↗
PubMed1993

Active avoidance behavior using pontine nucleus stimulation as a conditioned stimulus in the rat.

Five groups of rats were trained in an active avoidance task in a shuttle box with different conditioned stimuli. Animals with either a light-conditioned stimulus or with electrical stimulation of the ventral pontine nucleus as a conditioned stimulus rapidly learned to avoid an aversive event, while those with no conditioned stimulus, with electrical stimulation of the lateral pontine nucleus or the medial lemniscus did not learn to avoid. Therefore, stimulation of a specific subdivision of the pontine nucleus is as effective as a light-conditioned stimulus to learn an active avoidance task.

Animals↗
PubMed1993

Motor activity induced by disinhibition of the primary motor cortex of the rat is blocked by a non-NMDA glutamate receptor antagonist.

Application of a GABAA (gamma-aminobutyric acid-A) receptor antagonist through a microdialysis probe into the forelimb primary motor cortex of ketamine-anesthetized rats induced electromyographic activity in the contralateral forelimb. This activity consisted of spontaneous forelimb movements with a frequency of 0.8 +/- 0.2 Hz. The motor activity induced by GABAA receptor blockade was suppressed by application through the dialysis probe of a non-NMDA (N-methyl-D-aspartate) receptor antagonist, but not by an NMDA receptor antagonist. Glutamate eliminated the blocking effect of the non-NMDA receptor antagonist upon GABAA receptor blockade mediated activity. In conclusion, the results show that an excitatory input to the motor cortical output is mediated through a non-NMDA receptor, therefore the effects of cortical disinhibition may be controlled by non-NMDA receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1993

Reversal of paw preference after ablation of the preferred forelimb primary motor cortex representation of the rat depends on the size of the forelimb representation.

Animals were tested for forelimb preference in a grasp or in a force task before microstimulation mapping of the primary motor cortex contralateral to the preferred forelimb. The size and location of the preferred forelimb primary motor cortex representation was determined and ablated. Seven days later, forelimb preference was again evaluated. Reversal of the initial preference after cortical ablation depended on the size of the preferred forelimb primary motor cortex representation. The mean size of the forelimb representation of the animals that immediately reversed forelimb preference after the cortical ablation was significantly smaller than the mean size of the representation of the animals that did not reverse forelimb preference in three consecutive tests seven days after the lesion. In another experiment, the size, location, and threshold currents of the forelimb representations were evaluated bilaterally before the forelimb preference test. The mean size of the preferred representations did not differ from the mean size of the non-preferred representations. However, when the primary motor cortex representation of the preferred forelimb was ablated, reversal of the initial preference depended, as in the previous experiment, on the size of the forelimb representation. In conclusion, reversal of forelimb preference after ablation of the preferred forelimb primary motor cortex representation depends on the size of the forelimb representation. Moreover, forelimb preference in a behavioral task is not associated with a larger forelimb representation in the contralateral primary motor cortex.

Animals↗
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

Facilitation and recovery of shuttle box avoidance behavior after frontal cortex lesions is induced by a contingent electrical stimulation in the ventral tegmental nucleus.

A bilateral ablation of the frontal cortex was performed in rats before and after training in an active avoidance task in a shuttle box. Animals with this lesion showed an impairment in learning and in the reversal of the avoidance task. If the animals with the lesion were implanted with an electrode in the ventral tegmental nucleus and received an electrical stimulation in this area contingent to a correct response (avoidance or escape response) in the behavioral task, they did not show any impairment in the performance of the task. Furthermore, the effect of the stimulation persisted after it was retrieved. The present findings indicate that the motivational and cue properties of the electrical stimulation of the ventral tegmental nucleus may serve to facilitate learning and reversal in an avoidance task and to induce at the long term a recovery process in animals in which the frontal cortex has been ablated. Therefore, this method may be useful to study the adaptative changes which take place in the nervous system after recovery from brain damage occurs.

Animals↗
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

Performance in an escape task induces fos-like immunoreactivity in a specific area of the motor cortex of the rat.

The expression of the c-fos proto-oncogene was studied in two different areas of the motor cortex and in the hippocampus of the rat after performance in an escape task in a Skinner box. Performance in this task caused an increase in the number of cells showing fos-like immunoreactivity in layers V and VI of the forelimb motor-sensory cortex with respect to yoked animals which had received the same amount, frequency and duration of aversive stimulation and manipulation as the trained animals. Therefore, this increase is the specific effect of performing the behavioral task. In the hindlimb motor-sensory cortex there were no differences between the trained and the yoked animals in any of the cortical layers. No differences were observed in the dentate gyrus of the hippocampus between trained and yoked animals, while the control animals showed a much lower fos-like immunoreactivity. In conclusion, infragranular layers in the forelimb representation of the primary motor cortex become activated with respect to the expression of fos-like immunoreactivity after performance in an escape task in a Skinner box. This result is consistent with the idea that even in complex structures such as the cerebral cortex, specific trace systems become activated for the performance of complex behavioral tasks.

Analysis of Variance↗
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↗