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Biomedical subjects

F Chaouloff

Publications and source records attributed to F Chaouloff.

At least 55 records · Page 3Linked to original sources
PubMed1995

Cortical [3H]ketanserin binding and 5-HT2A receptor-mediated behavioral responses in obese Zucker rats.

Past studies have indicated that genetically obese Zucker (fa/fa) rats are hypercorticoid, and that this neuroendocrine alteration plays a key role in the syndrome. In keeping with the proposal that glucocorticoids may upregulate central 5-HT2A receptors, we have studied the effects of acute and repeated 5-HT2A receptor stimulation by 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane (DOI) in lean and obese Zucker rats. Acute injection of DOI (2 mg/kg, SC) elicited a lower number of head shakes in obese rats compared to that measured in lean rats. Conversely, neither DOI-elicited decreases in food intakes and body weights nor cortical [3H]ketanserin binding were affected by obesity. In rats repeatedly pretreated with DOI, biochemical and functional indices of 5-HT2A receptor downregulation failed to reveal an effect of obesity. It is suggested that 5-HT2A receptor-mediated functions, but not their downregulation, may be differentially affected in the hypercorticoid obese Zucker rat.

Amphetamines↗
PubMed1995

Regulation of 5-HT receptors by corticosteroids: where do we stand?

Twenty five years ago, experimental procedures such as adrenalectomy and corticosteroid administration (to intact rats) allowed the recognition of direct and indirect controls of central 5-HT synthesis rate by corticosteroids. These effects indicated that the activity of the hypothalamo-pituitary-adrenal (HPA) axis, whether under basal conditions or during stress, is endowed with a modulatory action upon serotonergic neurons. Nowadays, in situ hybridisation, in vitro autoradiography, and radioligand binding on the one hand, and electrophysiological, behavioural, and neuroendocrinological responses on the other hand, are tools that allow the analysis of direct corticosteroid effects upon 5-HT receptors. Among the dozen of 5-HT receptors identified so far, four receptors (namely the 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT2C receptors)--and the 5-HT uptake system--have been the focus of studies aimed at detecting corticosteroid modulatory effects. The results that are reviewed herein indicate that hippocampal 5-HT1A receptors are under the tonic inhibitory control of corticosterone. This control is directly exerted at the level of the 5-HT1A receptor gene, essentially through mineralocorticoid receptors; as well, electrophysiological findings bring support for an additional modulation of hippocampal 5-HT1A receptor-mediated functions by indirect (ie 5-HT1A receptor gene-independent) genomic actions of corticosteroids. In keeping with the respective effects of stressful stimuli and psychotropic drugs upon the HPA axis and central serotonergic systems, it is likely that these corticosteroid-5-HT1A receptor interactions in the hippocampus have consequences in the pathophysiology of mood disorders. However, because the data regarding a corticosteroid control of other 5-HT receptors are either scarce and contradictory (eg 5-HT1B, 5-HT2A, 5-HT2C receptors and 5-HT uptake systems) or lacking, it is at the present time unknown whether corticosteroids exert other effects on 5-HT receptor-mediated functions, including those related to homeostasis.

Adrenal Cortex Hormones↗
PubMed1994

Paradoxical differences in animal models of anxiety among the Roman rat lines.

The Roman high-avoidance (RHA) and low-avoidance (RLA) rat lines have been selected upon their divergent active avoidance behaviours. On the basis of open-field behavioural analyses, it has been suggested that RLA rats display more emotionality than RHA rats. Herein, we have analysed the behaviours of male RHA and RLA rats in three tests putatively related to anxiety, namely the elevated plus-maze, the black/white box, and the social interaction test. In the elevated plus-maze, neither the number of total arm entries nor the percent number of open arm entries were different between the Roman lines. Alternatively, RLA rats spent more time on the open arms, compared to RHA rats. In the black/white box, both the latency to enter the black compartment, the number of shuttles, the time spent in the white compartment, and the general activity in the white compartment were higher in RLA rats, compared to their RHA counterparts. Lastly, socially isolated RHA and RLA behaved similarly when exposed to a social interaction test. It is suggested that under particular experimental conditions male RLA rats display less anxiety than male RHA rats, and that the open-field test may provide indices of activity rather than indices of anxiety.

Animals↗
PubMed1994

Influence of physical exercise on 5-HT1A receptor- and anxiety-related behaviours.

Treadmill exercise (1 h at 20 m/min) has been shown to increase brain serotonin (5-HT) synthesis/metabolism in 4-day trained rats. This work has analysed whether these changes are associated with (5-HT-dependent or -independent) alterations in pre- and postsynaptic 5-HT1A receptor-mediated behaviours; in addition, the controversial hypothesis that exercised rats are less anxious than sedentary rats was tested in the elevated plus-maze and the social interaction models. Acute administration of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.125-0.5 mg/kg) triggered hyperphagia, forepaw treading, and flat body posture, the amplitude of which were not affected by training or acute exercise. In the elevated plus-maze, training, but not acute exercise, reduced the number of total arm entries. In the social interaction test, trained and acutely exercised rats displayed increased locomotion and decreased defecation, compared to resting rats, but social interaction and rearings were not affected. It is suggested that the aforementioned effects of acute exercise upon 5-HT synthesis/metabolism in short-term trained rats are not associated with changes in 5-HT1A receptor- and anxiety-related behaviours.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Effects of repeated 2-deoxy-D-glucose administration on ingestive, psychological, and 5-HT-related behaviours in the rat.

The effects of repeated treatment with the metabolic stressor 2-deoxy-D-glucose (2-DG: 500 mg/kg/day, 7 days) upon some ingestive and psychological behaviours were investigated, and compared with those elicited by repeated immobilization or cold exposure (2 hr/day, 7 days). Because all these stressors affect central serotonergic systems, 5-HT1A and 5-HT2A receptor-mediated behaviours were also analysed. Both 2-DG administration and immobilization decreased daily food intakes and increased the weight of the adrenals, while all stressors reduced body weight gain. In addition, 2-DG triggered hyperphagia (and reduced body weight loss) throughout the 7 light phases, and hypophagia (and reduced body weight gain) throughout the 7 dark phases. However, the other stressors had only temporary effects during the light phases. These results suggested that immobilized and cold exposed rats, but not 2-DG-treated rats had progressively adapted to their stressors. Furthermore, 2-DG-treated rats exhibited decreased ambulation when placed in the open field, but no change in social interaction. Forepaw treading and flat body posture responses to the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) were not altered by the stressors, but both of them slightly amplified 8-OH-DPAT-induced hypothermia. This change was associated with a decreased head shake response to the 5-HT2A agonist 1-(4-iodo-2,5-dimethoxy-phenyl)-2-aminopropane (DOI) in 2-DG-treated rats, compared with that measured in the other groups. This study opens the possibility that alterations in feeding rhythms has functional consequences on 5-HT2A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Glucose, insulin, and open field responses to immobilization in nonobese diabetic (NOD) mice.

Numerous studies have suggested that stress precipitates type I diabetes. Because stress-elicited hyperglycemia may play a role in this effect, we measured the influence of acute immobilization (90 min) upon plasma glucose and insulin levels in nonobese diabetic (NOD) mice, a spontaneous model of type I diabetes. To this end, prediabetic 8-week-old mice of both sexes were compared to age- and sex-matched C57BL/6 control mice. Baseline plasma glucose levels and immobilization-elicited hyperglycemia were both lower in male and female NOD mice compared to their C57BL/6 counterparts. However, the maximal effects of immobilization upon plasma insulin (and corticosterone) levels were not different between NOD and C57BL/6 mice. When subjected to a metabolic stressor, such as 2-deoxyglucose-induced neuroglucopenia, both strains responded with similar increases in plasma glucose levels. This change was associated with hyperinsulinemia, whose amplitude was lower in NOD than in C57BL/6 females. Lastly, administration of the alpha 2-adrenergic agonist, clonidine, elicited a marked increase in plasma glucose levels, whose amplitude was independent of the strain. The results from this study indicate that the two strains differed in their glycemic response to a psychological, but not to a metabolic, stressor. Because NOD mice were found to exhibit increased locomotion when placed for the first time in an open field, it is suggested that behavioral differences contribute to this differential effect of immobilization upon circulating glucose levels in NOD and C57BL/6 mice.

Animals↗
PubMed1994

Effects of chronic lard feeding on sympathetic nervous system activity in the rat.

The level of sympathetic nervous system (SNS) activity in obesity is controversial, with reports claiming either increased or decreased SNS activity. The following studies examined SNS activity in a dietary form of obesity, ingestion of a lard-enriched diet for 4 wk. Plasma norepinephrine (NE) levels were 61% higher in rats fed the lard-enriched diet than in chow-fed controls at 20 degrees C (200 +/- 24 pg/ml vs. 124 +/- 6, P < 0.005) and remained elevated after 1 h of cold exposure (4 degrees C). [3H]NE turnover was markedly increased in heart, but not in interscapular brown adipose tissue (IBAT), kidney, liver, skeletal muscle, or spleen of rats fed the high-fat diet. By contrast, ingestion of a diet similarly enriched with sucrose raised rates of [3H]NE turnover in IBAT as well as in heart. Thus chronic ingestion of a lard-enriched diet induces region-specific stimulation of SNS activity that is greater in heart than in IBAT. Whereas the absence of an SNS response to lard in IBAT may contribute to weight gain in these animals, activation of cardiac sympathetic nerves may promote development of hypertension in this model of obesity.

Acclimatization↗
PubMed1994

Failure to find behavioural differences between lean and obese Zucker rats exposed to novel environments.

Past studies have evidenced a key role for hypercorticism in the obesity syndrome of the Zucker (fa/fa) rat. Here, the hypothesis that obesity-related hypercorticism is associated with increased anxiety/emotionality was tested in the elevated plus-maze, the black/white box, and the open field. In the elevated plus-maze, none of the parameters examined (open arm entries, time in open arms, total number of entries) differed between lean (Fa/?) and obese (fa/fa) rats. In addition, neither the behaviours measured in the black/white box (latency to enter the black compartment, number of transitions, time spent in the white compartment, locomotion, rearing) nor those measured in the open field (locomotion, rearing, grooming, defecation) were affected by obesity. This study suggests that obesity-related hypercorticism in fa/fa rats is not associated with indices of emotionality and anxiety, at least those analysed by means of the tests used here.

Adrenocortical Hyperfunction↗
PubMed1993

Behavioural and biochemical evidence that glucocorticoids are not involved in DOI-elicited 5-HT2 receptor down-regulation.

Numerous studies have brought evidence for reciprocal relationships between glucocorticoids and 5-HT2 receptors; however, whether glucocorticoids affect 5-HT2 receptor regulation is still unknown. Herein, we have analyzed whether 5-HT2 receptor down-regulation following repeated administration of the 5-HT2/5-HT1C receptor agonist 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane (DOI) is affected by glucocorticoid removal. Compared with sham surgery, adrenalectomy (11-15 days beforehand) did not affect either frontal cortex [3H]ketanserin binding nor the number of head shakes elicited by a single administration of DOI (2.5 mg/kg s.c.). Pretreatment with DOI (2.5 mg/kg s.c. x 4 in 48 h) decreased to similar extents the head shake response to DOI injection in sham (-88%) and adrenalectomised (-95%) rats. Confirmingly, this paradigm was found to diminish the Bmax for [3H]ketanserin binding in sham and adrenalectomised rats by 64% and 46%, respectively. From these data, it is concluded that glucocorticoid removal does not alter 5-HT2 receptor binding and function nor does it affect 5-HT2 receptor down-regulation.

Adrenalectomy↗
PubMed1993

Corticosterone response to the serotonergic agonist D-fenfluramine may be independent from corticotropin-releasing factor (CRF).

This study was designed to assess the involvement of corticotropin-releasing factor (CRF) in the corticosterone response to the acute administration of the serotonergic indirect agonist D-fenfluramine in the rat. In addition to plasma corticosterone, D-fenfluramine-induced hyperglycemia (which is independent from the hypothalamo-pituitary-adrenal axis) was also analyzed. Acute i.v. injection of sheep anti-CRF antiserum (15 min beforehand) markedly diminished either stress-induced corticosterone release (but not ether stress-induced increases in plasma glucose levels), thereby indicating that passive immunization was efficient. Acute administration of D-fenfluramine (3 mg/kg i.v.) increased plasma corticosterone and glucose levels to similar extents in control rats (i.e. injected with normal sheep serum) and in anti-CRF antiserum-injected rats. These results indicate that, under our experimental conditions, D-fenfluramine-induced corticosterone elevation is of peripheral origin (through pituitary and/or adrenocortical pathways).

Animals↗
PubMed1993

Subchronic treatment with anxiolytic doses of the 5-HT1A receptor agonist ipsapirone does not affect 5-HT2 receptor sensitivity in the rat.

Acute stimulation of 5-HT1A receptors has been reported to diminish some 5-HT2 receptor-mediated responses in the rat, but there is controversy as to whether repeated stimulation of 5-HT1A receptors leads to identical changes. In this study, we tested the influence of repeated treatment with the 5-HT1A receptor agonist ipsapirone (0.5 g/l in drinking water for 21 days) on some 5-HT2 receptor-mediated responses elicited by the acute injection of the 5-HT1C/5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). These responses included hyperglycemia, corticosterone release, and head shakes; cortical 5-HT2 receptor number and DOI-induced prolactin release (a 5-HT1C/5-HT2 receptor-mediated event) were also analyzed. In a first series of experiments, ipsapirone administration for 1, 8, 15, and 20 days reduced the duration fo shock-induced ultrasonic vocalization. Ipsapirone administration for 21 days reduced fluid intake and decreased body weight, but did not affect baseline plasma glucose, corticosterone, and prolactin levels or cortical 5-HT2 receptor number. The increases in plasma glucose levels elicited by acute injection of either DOI (0.1-1 mg/kg i.v.) or clonidine (an alpha 2-adrenoceptor agonist; 0.05 mg/kg i.v.) were reduced in ipsapirone-pretreated rats. The maximal effects of DOI and clonidine on plasma corticosterone or prolactin levels were not affected by ipsapirone pretreatment. Ipsapirone decreased the area under the corticosterone curve in both DOI- and clonidine-treated rats. Lastly, the head-shake response to DOI (0.5-2 mg/kg s.c.) was similar in vehicle- and ipsapirone-pretreated rats. These data indicate that a 3-week treatment with anxiolytic doses of the 5-HT1A receptor agonist ipsapirone does not desensitize 5-HT2 receptors.

Administration, Oral↗
PubMed1993

5-HT1C/5-HT2 receptor blockade prevents 1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane-, but not stress-induced increases in brain tryptophan.

We have previously shown that acute administration of the 5-HT1C/5-HT2 receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane (DOI), elevates brain tryptophan levels. The present work aimed to investigate the mechanisms responsible for this elevation. Acute s.c. administration of a 2-mg/kg dose of DOI increased brain tryptophan levels but did not affect either plasma free tryptophan, plasma total tryptophan, brain 5-HT, or brain 5-hydroxyindoleacetic acid. Pretreatment with the 5-HT1C/5-HT2 receptor antagonist, LY 53857, prevented the DOI-induced increase in brain tryptophan levels, whilst the increase was reduced by the 5-HT2 receptor/alpha 1-adrenoceptor antagonist, ketanserin, and to a lesser extent, by the ganglionic blocker, chlorisondamine. On the other hand, pretreatment with either the peripherally acting 5-HT1C/5-HT2 receptor blocker, BW 501C67, the 5-HT uptake enhancer, tianeptine, the 5-HT uptake blocker, paroxetine, or the beta 2-adrenoceptor antagonist, ICI 118.551, proved ineffective. Lastly, pretreatment with LY 53857 did not affect the immobilization-induced elevation in brain tryptophan levels. It is concluded that the elevation in brain tryptophan levels induced by DOI but not that induced by stress is due to central 5-HT1C and 5-HT2 receptor stimulation.

Adrenergic beta-Antagonists↗
PubMed1993

Psychoneuroendocrine outcomes of short-term crowding stress.

One-week exposure to crowding stress has been reported to affect body weight and pituitary-adrenal axis activity. This study has first evaluated whether the aforementioned changes are associated with altered exploratory activity. One-week crowding (16 rats/cage) diminished body weight gains, compared to the control situation (four rats/cage): actually, this difference was mainly due to a marked loss in food intake and body weight following the first day of crowding. On the other hand, 1-week crowded rats were not different from their controls when placed for the first time in an open field, as shown by the analysis of their exploratory activities, their number of grooming episodes, and their defecation. Psychoneuroendocrine effects of 1-day crowding were then investigated: actually, open field behaviors were not modified but basal plasma glucose levels were decreased. Moreover, neither plasma ACTH and corticosterone levels nor 2-min cold swim-induced increases in corticosterone levels were affected. Besides, cold swim-induced increases in plasma ACTH levels were amplified in crowded rats, and these increases were associated with hyperglycemia in crowded, but not in control rats. It is suggested that 1-day exposure to crowding has differential consequences upon feeding and exploratory behaviors while potentiating the responsiveness of stress hormones.

Adrenocorticotropic Hormone↗
PubMed1993

Effects of tianeptine on 5-HTP- and dextrofenfluramine-induced hypophagia in the rat.

The aim of this work was to analyze whether tianeptine, a 5-hydroxytryptamine (5-HT) reuptake enhancer, opposes the loss in food intake elicited by 5-HT release. Rats were food deprived for 20 h, pretreated either with saline or 7-[3-chloro-6-methyl-5, 5-dioxo-6,11-dihydro- (c,f)-dibenzo-(1,2-thiazepine)-11-yl-amino]-heptanoic acid (tianeptine, 10 mg/kg, IP), and injected 1 h afterwards either with saline, with the 5-HT precursor L-5-hydroxytryptophan (5-HTP, 20 or 40 mg/kg, IP), or with the 5-HT reuptake inhibitor/5-HT releaser dextrofenfluramine (d-FEN, 1.5 or 3 mg/kg, IP). Diets were then presented 30 min later, and individual food intakes were measured 1, 2, 3, and 4 h after food presentation. Saline- and tianeptine-pretreated saline-injected rats ate the most, and to a similar extent, during the first hour of food presentation; however, in these animals tianeptine pretreatment tended to diminish rates of eating throughout the last 3 h of analysis. Administration of 5-HTP or d-FEN triggered immediate dose-dependent decreases in food intake that were not affected by tianeptine pretreatment. In addition, tianeptine pretreatment did not alter either brain d-FEN or d-norfenfluramine levels, thereby suggesting that the lack of effect of tianeptine against d-FEN-elicited hypophagia could not be accounted for by changes in d-FEN metabolism. This study opens the possibility that tianeptine counteracts the effects of 5-HT release in some paradigms but not in others.

5-Hydroxytryptophan↗
PubMed1993

Chronic treatment with an anxiolytic dose of the 5-HT1A agonist ipsapirone does not alter ipsapirone acute neuroendocrine effects.

We recently reported that chronic administration of the 5-HT1A receptor agonist, ipsapirone (0.5 milligrams in drinking water for 3 weeks), has anxiolytic activity in the rat. Herein, we investigated whether this treatment promotes tachyphylaxis to the acute neuroendocrine effects of ipsapirone. Rats chronically treated with ipsapirone displayed a 7% decrease in body weights, compared to vehicle-pretreated rats, thereby confirming previous observations. On the other hand, ipsapirone pretreatment did not affect basal plasma levels of adrenocorticotropin (ACTH), corticosterone, prolactin, aldosterone, and renin activity, nor did it affect their respective rises following an acute ipsapirone (50 mg/kg PO) challenge. Moreover, ipsapirone pretreatment did not affect the increase in plasma prolactin levels elicited by the dopaminergic receptor antagonist haloperidol. These results suggest that neither the 5-HT1A receptors nor the catecholamine receptors that mediate ipsapirone acute neuroendocrine effects develop tolerance to stimulation upon sustained ipsapirone treatment.

Adrenocorticotropic Hormone↗
PubMed1993

Are 5-HT1A autoreceptors involved in the inhibitory effect of ipsapirone on cold-elicited thyrotropin secretion?

Administration of the serotonin (5-HT)1A receptor agonist ipsapirone has been shown to decrease cold-elicited thyrotropin (TSH) secretion. We have analyzed (1) the influence of 5-HT1A receptors and ipsapirone metabolism into 1-(2-pyrimidinyl)-piperazine (1-PP, an alpha 2-adrenoceptor antagonist) on the effect of ipsapirone on TSH release, and (2) the interaction between the corticosterone-releasing effect of ipsapirone and its inhibitory influence on TSH release. Pretreatment with proadifen (50 mg/kg, 5 h before ipsapirone), i.e. an inhibitor of ipsapirone metabolism into 1-PP, did not affect ipsapirone-induced inhibition of cold-elicited TSH secretion. Pretreatment (15 min before ipsapirone) with the 5-HT1/5-HT2 receptor antagonist metergoline 2 mg/kg) or with the 5-HT1A receptor blocker (-)-pindolol (5 mg/kg) increased baseline and cold-elicited TSH release but the inhibitory influence of ipsapirone on cold-elicited TSH release was alleviated by (-)-pindolol pretreatment only. Cold exposure increased corticosterone release, an effect which was insensitive to (-)-pindolol pretreatment. Lastly, pretreatment with the 5-HT synthesis inhibitor p-chlorophenylalanine prevented the immediate inhibitory effect of the selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) upon cold-induced TSH release, but it amplified the late release of TSH in cold-exposed 8-OH-DPAT-injected rats. These results suggest that presynaptic 5-HT1A receptors mediate ipsapirone-induced inhibition of cold-elicited TSH release, an effect which may be partially opposed by postsynaptic 5-HT1A receptor stimulation.

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