[Show abstract][Hide abstract] ABSTRACT: In a parallel study in 10 individual rats, three time series of plasma concentrations of ACTH, corticosterone (CORT), and interleukin-1� (IL-1�) were measured before (time 0) and at intervals between 15 and 480 mm following intra-arterial (i.a.) infusions of 25�tg/kg lipopolysaccharide (LPS). All LPS injections were given at 9 AM. The first time series was performed on naive rats (day 1 ). A se- quence of six daily injections (days 3-8) of the same dose of LPS followed. The post-LPS time course of the plasma ACTH, CORT and IL-1�3 levels were studied on days 3 (second injection) and 8 (seventh injection). The first LPS injection induced a rapid (30 min) eightfold rise in plasma ACTH and CORT, culminating in concentrations 30 times the baseline at 60 nlin (ACTH) and 15 times baseline at 120 min (CORT). Both hormones receded back to the initial basal level at 480 miii. On the other hand, IL-1�3 increased slowly to peak at 13 times baseline 120 mm before declining to minimal seven- to ninefold basal levels, 480 mm and even 48 h post-LPS. During the second phase of the experiment starting 48 h after the initial LPS priming sequence, the ACTH and CORT responses to daily recurrent LPS injections again differed from those of IL-1�. The post-LPS time courses of the ACTH and CORT reaction dis- played a typical pattern of a progressive attenuation studied at days 3 and 8. The peak amplitudes at days 3 and 8 were reduced to 60 and 10%, respectively, for ACTH, and to 85 and 45% for CORT of those observed at the first LPS test. The duration of the response (both) was also shortened from 480 mm (first LPS test) to 300 mm at days 3 and 8. The post-LPS patterns of the IL- 1 � responses were char- acterized, first by basal levels seven to nine times higher than the initial baseline values (day 1), and by a rapid suppression of the post-LPS response, with only a slight (30%) increase at day 3 and no increase at day 8. Thus, after both acute and recurrent LPS administration, ACTH/CORT and IL-1� reacted dif- ferently to the endotoxin challenge. The two LPS reactive systems were not correlated. This is incon- sistent with the often proposed role of increased plasma IL- 1 � release as an intermediary factor in the LPS-induced recruitment of the corticotropic axis in general infections. J. Leukoc. Biol. 59: 341-346; 1996.
[Show abstract][Hide abstract] ABSTRACT: This article is to give an outline on some scientific experiments on the effects of the posttraumatic stress disorder (psychic factors) on the variations neuroendocriniennes (adrenal and prolactinic). The prolactin and cortisol responses to dexamethasone (0.5mg) were studied in masculin subject posttraumatic stress disorder (PTSD) (n=10), normal controls (n=18) and non PTSD subjects (n=10), in order to better determine these interactions. Both the two groups of subjects which lived events of everyday life extremely stressing (PTSD and not PTSD) showed an enhanced cortisol suppression in response to dexamethasone than the normal subjects. In contrast, only the PTSD showed an hypersuppression of cortisol to the dexamethasone. These findings suggest that the prolactin response to dexamethasone in the non PTSD subjects can reflect a predictive indicator of occurred of the PTSD.
[Show abstract][Hide abstract] ABSTRACT: Glucocorticoid receptors are widely distributed in the cochlea but their role remains poorly known. Previous studies provided contradictory reports on a possible cochlear acoustic hypersensitivity induced by adrenal insufficiency, while several experiments agree on a significant action of glucocorticoid receptors in adverse conditions such as acoustic trauma and restraint stress. The present experiments confirmed a cochlear acoustic hypersensitivity induced by adrenalectomy and reversed by corticosterone supplementation. These observations point to a significant role of corticosteroids in basal cochlear functioning. The glucocorticoids are known to be essential for limiting and resolving inflammatory processes. The endotoxin Escherichia coli lipopolysaccharide is widely used to induce inflammatory reactions. However, in various organs several toxic processes of this endotoxin are not influenced by glucocorticoids. From previous experiments on the cochlea there is no evidence that glucocorticoids are an essential factor against endotoxin cochlear toxicity. In the present experiments it was found that adrenalectomy greatly increased the cochlear susceptibility to endotoxin; the effect was reversed by providing corticosterone supplementation. This shows the essential role of corticosterone in this cochlear inflammation model. In previous studies local administration (at the cochlear base) of endotoxin was used and losses of cochlear acoustic sensitivity were found predominantly at high frequencies; in contrast, the systemic injection used in this study produced a cochlear loss of acoustic sensitivity at all frequencies, indicating a uniform cochlear sensitivity to the toxic effects of endotoxin.
European Journal of Neuroscience 01/2007; 24(12):3365-71. DOI:10.1111/j.1460-9568.2006.05224.x · 3.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hexachlorobenzene (HCB) is a dioxin-like compound widely distributed in the environment. In this study, we investigated the effects of HCB on the cochlea. Conscious free-moving rats were given HCB per os daily for 4 weeks at doses of 0.16, 4 or 16 mg/kg in olive oil, whereas the control group received olive oil only. The effects of HCB were evaluated at various time intervals, by measuring auditory nerve acoustic thresholds and plasma thyroid hormone concentration by radioimmunoassay. Histological evaluation involved surface preparation and scanning electron microscopy observations of cochlear hair cells. At a dose of 0.16 mg/kg, HCB induced no loss of acoustic sensitivity, whereas at 4 mg/kg, it induced cochlear sensitivity deficits at the mid-frequencies (2-16 kHz) with complete recovery once treatment was stopped. At a dose of 16 mg/kg, permanent threshold shifts were observed at all frequencies tested (from 1 to 32 kHz). Morphological studies showed no cochlear hair cell loss or alteration of stereocilia. HCB treatment reduced circulating thyroxine concentrations. Thyroidectomy had no effect on cochlear sensitivity in control animals. Thus, HCB is a potent oto-toxicant, and its ototoxicity may be independent of its thyroidal effects.
Hearing Research 06/2004; 191(1-2):125-34. DOI:10.1016/j.heares.2003.12.017 · 2.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Subcutaneous melatonin implants were inserted in mink subjected to natural (autumn) or experimental gonadostimulatory short-days (4L:20D), after lesion of the suprachiasmatic nucleus (SCNx) or after superior cervical ganglionectomy (SCGx). Gonad stimulation was assessed by measuring testicular volume and plasma testosterone level. In SCNx and SCGx animals, all measurements were indicative of sexual quiescence. In contrast, both SCNx and SCGx animals with melatonin, maintained in natural or experimental gonadostimulating short-days, showed an increase in testicular activity 2 months after melatonin implantation. Thus, melatonin (and pineal activity) is a prerequisite for the photoperiodic stimulation of reproductive activity, and the SCN is not necessarily the target site for melatonin action on the renewal of reproduction in the mink.
Journal of Pineal Research 02/2002; 32(1):15-20. DOI:10.1034/j.1600-079x.2002.10807.x · 9.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The glucagon response to insulin-induced hypoglycaemia was tested in rats that had been pinealectomised (Px), pinealectomised and fitted with melatonin implants (Px + MLT), or sham-operated (SO). The glucagon response to hypoglycaemia observed in SO rats (216 +/- 27 pg x ml(-1) at baseline versus 397 +/- 35 pg x ml(-1) at the hypoglycaemic peak, mean +/- S.D.) was stronger than that in Px rats (180 +/- 37 pg x ml(-1) and 229 +/- 21 pg x ml(-1), respectively) and weaker than that in Px + MLT rats (256 +/- 19 pg x ml(-1) and 516 +/- 11 pg x ml(-1), respectively). Our data indicate that the capacity to release glucagon during insulin-induced hypoglycaemia is altered in pinealectomised rats.
[Show abstract][Hide abstract] ABSTRACT: beta-Phenylethylamine (PEA) is a trace neuroactive amine implicated in the regulation of the hypothalamic-pituitary-adrenal (HPA) response to stress. To test this hypothesis, effects of subchronic levels of PEA (50 mg/kg/day treatment for 10 days) on the corticotroph function were studied. PEA treatment induces: (i) a significant increase of corticotrophin releasing hormone (CRH) immunoreactivity in the median eminence (ME), as measured by semi-quantitative immunofluorescence labeling techniques, (ii) a significant increase in CRH mRNA levels in paraventricular nuclei, as detected by in situ hybridization, and (iii) an increase in plasma adreno-corticotrophin hormone (ACTH) and corticosterone levels in responses to stress. PEA treatment has no effect on the number of binding sites and on the dissociation constant of the glucocorticoid receptors in any structure studied. Results of the dexamethasone suppression test were similar in PEA- and saline-treated rats. Taken together, these results suggest that PEA treatment stimulated the HPA axis activity levels directly via the CRH hypothalamic neurons, without altering the negative feed back control exerted by the glucocorticoids.
[Show abstract][Hide abstract] ABSTRACT: We have investigated whether the serotonin system participates in the mechanisms underlying the corticotropic response in experimentally infected rats. Intra-arterial injection of lipopolysaccharide (LPS; 25 microg/kg b.w.) resulted in a slight but significant increase in serotonin (5-HT) metabolism, detectable 60 min after the stimulus and lasting more than 480 min. Adrenocorticotropin (ACTH) and corticosterone (CORT) responses in intact rats conformed to earlier reports, increasing as early as 30 min after LPS injection and reaching maximal concentrations in the circulation 60 min after the bacterial endotoxin injection. Plasma concentrations of interleukin-1beta (IL-1beta) increased only after 60 min, reaching maximal levels 120 min after LPS. Depletion of hypothalamic 5-HT (-93%) by pretreatment of the animals with para-chlorophenylalanine (p-CPA), resulted in a halved ACTH response to LPS, despite an overall unchanged secretory pattern. Neither CORT nor IL-1beta secretory patterns were affected in these rats pretreated with p-CPA. Complete bilateral electrochemical lesions of the suprachiasmatic nucleus (SCN), which is innervated by mesencephalic 5-HT, impaired the early phase of the ACTH (-75% at 30 min) and CORT (-40% at 30 min) responses but did not affect the later increases of the corticotropic and the plasma IL-1beta responses following the LPS injection. These results indicate that serotonin pathways and SCN are involved in the earlier mechanisms of corticotropic axis recruitment following systemic LPS endotoxemia.
Journal of Neuroendocrinology 09/1999; 11(8):629-36. DOI:10.1046/j.1365-2826.1999.00374.x · 3.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The bilateral olfactory bulbectomy resulted in significantly higher plasma concentration of corticosterone, but not of ACTH in basal conditions and much higher plasma ACTH and corticosterone concentrations after 15 min of immobilization stress than were observed in sham-operated animals. Daily treatment with fluoxetine-a specific serotonin reuptake inhibitor-(15 mg/kg/day) had no effect on basal ACTH and corticosterone concentrations in OB rats. Fluoxetine treatment caused lower levels of ACTH, but not of corticosterone secretion, in response to immobilization stress. Bulbectomy significantly reducing 5-HT concentration in the amygdala. Stress increased serotonergic activity in the hypothalamus but not in the amygdala of OB rats. Chronic fluoxetine treatment of both unstressed and stressed OB rats resulted in a lower turnover rate in the two structures. Our results suggest that the hypercorticosteronemia observed after bulbectomy in unstressed OB rats is independent of the serotonergic system in both hypothalamus and amygdala. In contrast, they also demonstrate hypothalamic 5-HT changes in the HPA hyperactivity of OB rats in response to stress. Chronic fluoxetine treatment may normalize pituitary ACTH secretion in response to stress, possibly desensitization of the 5-HT receptors in the hypothalamus due to 5-HT being move available at the synapses.
[Show abstract][Hide abstract] ABSTRACT: Bilateral olfactory bulbectomy (OB) has drastic biochemical and behavioral effects and is often associated with an increase in plasma corticosterone concentrations. This experiment examined the effects of OB on adrenocorticotropin (ACTH) and corticosterone release under basal and stress conditions and on proopiomelanocortin (POMC) gene expression. Bulbectomy potentiated hypophysal ACTH and adrenal corticosterone release induced by ether stress but had no effect on ACTH release under basal conditions, despite a significant increase of circulating corticosterone. POMC gene expression was stronger (+60%) in OB rats than in sham-operated rats. These results suggest that olfactory bulbectomy substantially altered the negative feed-back exerted by glucocorticoids on anterior pituitary corticotropic cells in the male rat.
Hormone and Metabolic Research 08/1999; 31(7):399-401. DOI:10.1055/s-2007-978762 · 2.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bilateral olfactory bulbectomy (BOX) has major biochemical and behavioral effects, and is one of the most widely investigated of animal models of depression. We studied the consequences of BOX in male rats, on the organization of endogenous circadian rhythms for ACTH, corticosterone (Cort), motor activity (MA) and body temperature (BT). Mean levels were increased for Cort and MA, whereas no significant changes were observed for ACTH and BT. Significantly higher plasma Cort morning values were evidenced in BOX than sham-operated animals. In addition, compared with the single prominent power spectrum for the 24 hours period of control rats, the BOX animals displayed substantially lower 24 hours spectral power for the MA and BT circadian rhythms. These alterations suggest that olfactory bulbectomy, by disruption of the afferences and efferences, induced drastic changes in the function of the endogenous clock or of its regulating systems. From this point of view, bulbectomized rats may therefore be a valuable model to studying the etiology of psychiatric disorders with rhythm disturbance.
Archives of Physiology and Biochemistry 11/1997; 105(6):552-9. DOI:10.1076/apab.105.6.552.3273 · 1.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Corticotrophin-releasing hormone (CRH) immunoreactivity was detected in neurons of the central nucleus of the amygdala that were retrogradely labelled by injection of a fluorescent tracer (True Blue) into the paraventricular nucleus of the hypothalamus (PVN). The double-labelled neurons were located mainly in the medial subdivision of the central nucleus and appeared to comprise less than one-fifth of the descending pathway. These results suggest that CRH may act as a neurotransmitter in the amygdalo-hypothalamic pathway.
[Show abstract][Hide abstract] ABSTRACT: The regulatory role of the medial (CeM) or the lateral (CeL) part of the central nucleus of the amygdala on the hypothalamo-pituitary-adrenal axis response to stress was investigated in male rats. Basal and restraint- or lipopolysacharride (LPS)-induced plasma adrenocorticotrophic hormone (ACTH) levels were measured 7 days after sham operation or lesion of the CeM or CeL. CeM or CeL lesion did not change basal ACTH concentrations. In control rats, restraint or LPS injection induced a robust increase in ACTH secretion. CeL lesion did not modify the stress-induced increment in ACTH release. CeM lesion significantly decreased the ACTH response to restraint and potentiated the ACTH response to LPS injection. Our findings demonstrate that the CeM exerts complex influences on the corticotrophic response to stress, being either stimulatory or inhibitory, depending on the nature of the stressor.
[Show abstract][Hide abstract] ABSTRACT: The involvement of histaminergic transmission in the rapid and sustained plasma ACTH and corticosterone (CORT) responses induced in conscious rats by intra-arterial infusions of 25 micrograms.kg-1 Escherichia coli lipopolysaccharide (LPS) was investigated. LPS challenge produced a rapid and transient increase (+ 62%) in the amount of histamine (HA) in the median eminence 15 min after LPS administration, which contrasted with constant concentrations of plasma HA throughout the entire study (up to 480 min). Blockade of histaminergic receptors by intra-arterial pretreatment with H1 or H2 antagonists (mepyramine, 1 mg/rat, and cimetidine, 2 mg/rat), administered separately, did not affect either ACTH or CORT responses to LPS. Pretreatment with the same doses of the two antagonists in combination very significantly but transiently impaired the earliest phase (30 min) of the ACTH and CORT responses, without any apparent effect on the late phase of these responses. Pretreatment of the animals with an H3-receptor agonist (R alpha-methylhistamine dihydrochloride, 1 mg/rat) similarly blunted the early corticotropic responses to LPS, and also slightly depressed the long-lasting CORT response. These findings support the view that activated central HA transmission may be a key intermediate mechanism triggering the CRH41-ACTH-CORT responses to LPS, in addition to the previously demonstrated activating role of catecholaminergic afferences to the CRH41 neurons during this early complex phase of corticotropic response to LPS.
[Show abstract][Hide abstract] ABSTRACT: In a parallel study in 10 individual rats, three time series of plasma concentrations of ACTH, corticosterone (CORT), and interleukin-1 beta (IL-1 beta) were measured before (time 0) and at intervals between 15 and 480 min following intra-arterial (i.a.) infusions of 25 microgram/kg lipopolysaccharide (LPS). All LPS injections were given at 9 AM. The first time series was performed on naive rats (day 1). A sequence of six daily injections (days 3-8) of the same dose of LPS followed. The post-LPS time course of the plasma ACTH, CORT and IL-1 beta levels were studies on days 3 (second injection) and 8 (seventh injection). The first LPS injection induced a rapid (30 min) eightfold rise in plasma ACTH and CORT, culminating in concentrations 30 times the baseline at 60 min (ACTH) and 15 times baseline at 120 min (CORT). Both hormones receded back to the initial basal level at 480 min. On the other hand, IL-1 beta increased slowly to peak at 13 times baseline 120 min before declining to minimal seven- to ninefold basal levels, 480 min and even 48 h post-LPS. During the second phase of the experiment starting 48 h after the initial LPS priming sequence, the ACTH and CORT responses to daily recurrent LPS injections again differed from those of IL-1 beta. The post-LPS time courses of the ACTH and CORT reaction displayed a typical pattern of a progressive attenuation studied at days 3 and 8. The peak amplitudes at days 3 and 8 were reduced to 60 and 10%, respectively, for ACTH, and to 85 and 45% for CORT of those observed at the first LPS test. The duration of the response (both) was also shortened from 480 min (first LPS test) to 300 min at days 3 and 8. The post-LPS patterns of the IL-1 beta responses were characterized, first by basal levels seven to nine times higher than the initial baseline values (day 1), and by a rapid suppression of the post-LPS response, with only a slight (30%) increase at day 3 and no increase at day 8. Thus, after both acute and recurrent LPS administration, ACTH/CORT and IL-1 beta reacted differently to the endotoxin challenge. The two LPS reactive systems were not correlated. This is inconsistent with the often proposed role of increased plasma IL-1 beta release as an intermediary factor in the LPS-induced recruitment of the corticotropic axis in general infections.
Journal of Leukocyte Biology 04/1996; 59(3):341-6. · 4.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We previously showed that intra-arterial endotoxin infusion (lipopolysaccharide [LPS]: 25 micrograms.kg-1) induced an early (15 min) and sustained (480 min) rise in plasma ACTH associated with delayed (60-120 min) increases in plasma concentrations of TNF alpha, IL-6, and IL-1 beta. In the present study, we followed the post-LPS time-course of immunocytochemical expression of Fos-like activity in CRH41 neurons whose immunolabeling was enhanced by icv colchicine pretreatment 48 h before the LPS, and CRH41 release in the push-pull cannulated median eminence of free-moving rats, in parallel with the ACTH response. The earliest Fos-like activity in IR-CHR41 neurons was detected 30 min post-LPS. Colchicine strongly inhibited the LPS-induced activation of Fos expression in single-labeled paraventricular neurons. CRH41 release in the median eminence displayed a biphasic stimulation pattern, with a first peak (+60%) at 15 min together with the ACTH surge, followed by a second rise beginning at 45 min and lasting more than 2 h. Thus, the early stage of the ACTH surge following a nonlethal endotoxin challenge (< 60 min) already involves the activation of CRH41-producing neurons.
Molecular and Chemical Neuropathology 10/1995; 26(2):171-86. DOI:10.1007/BF02815011
[Show abstract][Hide abstract] ABSTRACT: We have recently shown that total lesion of the ventral noradrenergic bundle (VNAB-X), enhanced the short-lived (<120 min) triggering effect of intra-arterially (i.a.) given IL-1β on plasma ACTH levels. In the present study we used the same VNAB-X paradigm to explore the mechanisms of the long-lived (480 min) LPS stimulatory effect on plasma ACTH, corticosterone (CORT) and IL-1β levels. In control rats, 25 μg kg(-1) LPS induced a 20-fold increase in ACTH and a 7-fold increase in CORT concentrations at 30 min, which continued to rise until 60 min, before receding to baseline at 480 min. In contrast, the plasma IL-1β concentration started to increase above undetectable levels only at 120 min. In VNAB-X animals, the early (30 min) ACTH/CORT response to LPS was completely blunted, and the ACTH surge was reduced by 75% at 60 min. However, the sustained hormonal response (120 to 480 min) was unaltered. Both the temporal pattern and the amplitude of the plasma IL-1β response were normal. We conclude that (1) the VNAB is involved in the early (first 60 min) ACTH/CORT response to systemic LPS, (2) plasma IL-1β does not appear to be associated with this early corticotropic activation and (3) the later stages of the ACTH/CORT response to LPS (60 to 480 min) appear to be independent of the VNAB control and may therefore involve different control mechanisms, in which the IL-1β, by this stage massively released in the blood, may play a major role.