Biomedical subjects

P Broqua

Publications and source records attributed to P Broqua.

10 recordsLinked to original sources

PubMed1996

Antinociceptive effects of neuropeptide Y and related peptides in mice.

This study compares the antinociceptive and orexigenic activities of NPY and analogs after intracerebroventricular administration in mice. NPY had an antinociceptive action in the mouse writhing test which was not affected by prior treatment with naltrexone, yohimbine, idazoxan or reserpine. A detailed examination revealed that NPY (0.023-0.7 nmol), PYY (0.007-0.07 nmol), NPY2-36 (0.023-0.23 nmol) and the Y1 agonist [Leu31, Pro34]-NPY (0.07-0.7 nmol) all produced a dose-dependent and complete suppression of acetic acid-induced writhing. In contrast, the Y2 agonist, NPY13-36, had little or no antinociceptive effect. As shown by their ED50 values, the relative potency of the peptides was PYY > NPY2-36 > or = NPY > [Leu31, Pro34]-NPY > > NPY13-36, suggesting that a Y1 rather than a Y2 or Y3 receptor subtype was implicated in the antinociceptive action. Thereafter, all peptides were assessed for their effects on food intake. With respect to dose and peptide specificity, the hyperphagic effects of NPY and related peptides paralleled those on nociception, suggesting a common receptor mechanism. However, a purported NPY antagonist, [D-Trp32]-NPY, attenuated NPY's effect on feeding yet this same peptide elicited a dose-dependent inhibition of acetic acid-induced writhing, suggesting some molecular distinction between antinociception and stimulation of food intake.

Adrenergic alpha-Antagonists↗

PubMed1993

Antidepressant/anxiolytic ipsapirone inhibits cold-induced hypothalamic TRH release.

Acute administration of the serotonin (5-HT)1A receptor agonist ipsapirone has been previously shown to elicit a dose-dependent decrease of cold-elicited thyrotropin (TSH) secretion. Therefore, the aim of the present study was to evaluate, by means of a push-pull cannula implanted in the median eminence (ME), whether ipsapirone acts primarily through an inhibition of cold-elicited thyrotropin-releasing hormone (TRH) release. Ipsapirone administration (10 mg kg-1 i.p., 30 min before cold) prevented cold-elicited TRH release, thereby confirming the above hypothesis. In addition, this study further validates push-pull perfusion in the ME as a key tool for measuring TRH secretion in vivo.

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

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↗

PubMed1992

Effects of cold stress on some 5-HT1A, 5-HT1C and 5-HT2 receptor-mediated responses.

The purpose of the present study was to analyze the influence of stress (24-h cold exposure) on presynaptic 5-HT1A receptors, and on postsynaptic 5-HT1A, 5-HT1C and 5-HT2 receptors. Cold exposure for 24 h affected neither pargyline-induced decreases in 5-hydroxyindoleacetic acid (5-HIAA) levels in midbrain and rest of brain, nor plasma glucose and corticosterone levels. Treatment with the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.5-1 mg/kg), 3-5 h after the end of cold exposure triggered less intense flat body posture and forepaw treading in cold-exposed rats than in controls. On the other hand, 15- and 30-min plasma glucose responses to 8-OH-DPAT (0.25-0.5 mg/kg, 3-5 h after cold) or to the alpha 2-adrenoceptor agonist, clonidine (0.025 mg/kg), were not affected by cold, while the 15-min, but not the 30 min, plasma corticosterone response to 8-OH-DPAT was slightly amplified in cold-exposed rats. Cold exposure affected neither the inhibitory effect of 8-OH-DPAT (0.25-0.5 mg/kg, 3-5 h after cold) on midbrain 5-HIAA levels, nor the hypothermic effect of 8-OH-DPAT (0.5-1 mg/kg, 3-5 h after cold). Lastly, the hypoactivity elicited by the 5-HT1C receptor agonist, m-chlorophenyl-piperazine (1.5-3 mg/kg, 3-5 h after cold), or head shakes elicited by the 5-HT2 receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (1-2 mg/kg, 3-5 h after cold), were of similar intensities in control and in cold-exposed rats.

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

PubMed1992

The 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane increases brain tryptophan levels in the rat.

Earlier studies have indicated that the sympathoadrenal system and the corticotropic axis control brain levels of tryptophan (Trp), the precursor of 5-hydroxytryptamine (5-HT). We investigated the effects of 5-HT receptor agonists known to activate the sympathoadrenal system and/or the corticotropic axis on plasma and brain Trp levels. Neither the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.5 mg/kg s.c.), nor the 5-HT1C receptor agonist 1-(3-chlorophenyl)piperazine (mCPP, 2.5 mg/kg s.c.) affected plasma and brain Trp levels. The 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane (DOI, 0.5-2 mg/kg s.c.) increased brain Trp levels, an effect which was significant for the two highest doses used (1.5-2 mg/kg s.c.).

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

PubMed1992

Influence of the novel antidepressant tianeptine on neurochemical, neuroendocrinological, and behavioral effects of stress in rats.

Tianeptine is a novel tricyclic agent that activates the neuronal uptake of serotonin (5-hydroxytryptamine, 5-HT). Taking into account the antidepressant effect of tianeptine in animals and humans, we have measured the influence of a pretreatment with tianeptine (10 mg/kg IP 1 hr beforehand) on some consequences of a single 2-hr restraint stress session in male rats. Thus, we have analyzed (1) 5-HT metabolism in various brain regions and plasma glucose (an index of sympathoadrenal activity) and corticosterone levels at the end of stress, and (2) open field scores 18-19 hr after immobilization in saline- or tianeptine-pretreated rats. Tianeptine was found to leave unaltered stress-induced increases in cortical, hippocampal, hypothalamic, midbrain, and striatal serotonergic metabolism. Similarly, stress-elicited elevations in plasma glucose and corticosterone levels were not affected by tianeptine pretreatment. On the other hand, tianeptine pretreatment reversed stress-induced deficit in exploratory activity. To test whether the latter positive effect of tianeptine was associated with changes in plasma glucose and corticosterone levels during the early phase of stress, we have measured plasma glucose and corticosterone levels (at 0, 5, 15, 30, and 60 min) in resting and stressed (catheterized) rats. The results indicated that tianeptine pretreatment did not alter plasma glucose and corticosterone early responses to stress. Although this study confirmed the antidepressant effect of tianeptine, the neurochemical and neuroendocrinological mechanisms underlying this positive effect remain to be determined.

Animals↗

PubMed1992

Differential effects of the novel antidepressant tianeptine on L-5-hydroxytryptophan (5-HTP)-elicited corticosterone release and body weight loss.

Biochemical and behavioural experiments have indicated that the novel antidepressant tianeptine stimulates 5-hydroxytryptamine (5-HT) reuptake. The present study has explored the influence of acute tianeptine pretreatment upon corticosterone release and body weight loss following L-5-hydroxytryptophan (5-HTP) administration in conscious rats. Administration of 5-HTP (20 mg/kg i.v.) increased plasma corticosterone levels to a similar extent in rats pretreated either with saline or tianeptine (10 mg/kg i.p., 60 min beforehand). Besides, prior administration of benserazide (50 mg/kg i.p., 30 min beforehand), an inhibitor of peripheral aromatic L-amino acid decarboxylase, prevented 5-HTP-induced corticosterone release in both saline- and tianeptine-pretreated rats. However, combined administration of benserazide and 5-HTP decreased overnight body weight in saline-, but not in tianeptine-pretreated rats. These results suggest that tianeptine preferentially activates 5-HT reuptake in central serotonergic neurones.

5-Hydroxytryptophan↗

PubMed1991

Buspirone, ipsapirone and 1-(2-pyrimidinyl)-piperazine decrease cold-induced thyrotropin secretion in rats.

The aim of this study was to analyse the effects of the 5-HT1A receptor-related antidepressants/anxiolytics, buspirone and ipsapirone (1-10 mg/kg i.v.), and those of their common metabolite, the alpha 2-adrenoceptor antagonist, 1-(2-pyrimidinyl)-piperazine (1-PP, 1-10 mg/kg i.v.), on cold-induced thyrotropin (TSH) secretion in conscious catheterised rats. The effects of the centrally acting 5-HT1A receptor agonist, 8-hydroxy-2-(d-n-propylamino)tetralin (8-OH-DPAT, 0.1-1 mg/kg i.v.), and of the peripherally acting 5-HT1A receptor agonist, N,N-dipropyl-5-carboxamidotryptamine (DP-5-CT, 0.1-1 mg/kg i.v.), were also included in this study. Buspirone, ipsapirone, and 1-PP dose dependently decreased cold-induced TSH secretion throughout the 90 min of analysis. However, the preventive effect of 1-PP was reached with a lower dose (3 mg/kg) than that needed for the parent compound (10 mg/kg). 8-OH-DPAT administration diminished but did not prevent cold-induced TSH secretion, while only the highest dose of DP-5-CT diminished secretion (1 mg/kg). Lastly, the TSH-releasing hormone (TRH)-induced TSH secretion was left unaffected by either buspirone or ipsapirone pretreatment (10 mg/kg), but was diminished by 1-PP pretreatment (3 mg/kg). These data suggest that both central 5-HT1A receptors and alpha 2-adrenoceptors mediate the effects of azapirones on cold-induced TSH secretion.

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

PubMed1990

In vivo evidence that insulin does not inhibit hepatic tryptophan pyrrolase activity in rats.

Previous reports have indicated that insulin administration triggers an early increase in plasma tryptophan (TRP) levels in fasted rats. Then, the present study was undertaken to investigate the putative role of liver tryptophan pyrrolase (TPO) in this short-term effect of insulin. In 24 hr fasted rats, doses of insulin that triggered an increase in plasma TRP levels (i.e., 2-3 I.U./kg, 1 hr) did not alter either holoenzyme or total enzyme activity. In another series of experiments, the administration of insulin (2 I.U./kg) to 24 hr fasted rats promoted biphasic time effects on plasma TRP levels and liver TPO activity. Thus, insulin initially triggered a rise in plasma TRP (without any change in liver TPO activity) and then increased liver TPO activity whilst plasma TRP returned toward control levels. In addition, hypercorticosteronemia was evidenced throughout the first phasis. Lastly, the influence of insulin administration (2 I.U./kg) on fasting-induced TPO induction was analysed. Whereas fasting increased liver TPO activity in a time-dependent manner, insulin administration (2 I.U./kg, 30 min) did not modify either plasma TRP or liver TPO activity. The data reported herein bring evidence that the effect of insulin administration on circulating TRP is not mediated by an inhibition of hepatic TPO.

Animals↗