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C Moret

Publications and source records attributed to C Moret.

At least 37 records · Page 2Linked to original sources
PubMed1997

Effects of milnacipran and pindolol on extracellular noradrenaline and serotonin levels in guinea pig hypothalamus.

Milnacipran, a dual noradrenaline (NA) and serotonin (5-hydroxytryptamine, 5-HT) uptake inhibitor, increased extracellular levels of NA and 5-HT in hypothalamus of freely moving guinea pigs as measured by microdialysis. The basal levels of both monoamines, which were tetrodotoxin sensitive, were increased in a dose-dependent manner and to a similar extent after the intraperitoneal administration of milnacipran (10 and 40 mg/ kg i.p.). Levels of the NA metabolite 4-hydroxy-3-methoxyphenylglycol (MHPG) were decreased by milnacipran at 10 and 40 mg/kg i.p., whereas those of the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) showed no effect. Subcutaneous injection of 5-HT1A and beta-adrenergic receptor antagonist (-)-pindolol alone, at 10 mg/kg, had no effect on the extracellular levels of NA or 5-HT. The concomitant administration of (-)-pindolol (10 mg/kg s.c.) with milnacipran (10 mg/kg i.p.) increased severalfold the effect of milnacipran on the extracellular levels of NA and 5-HT. These results indicate that milnacipran, by blocking the uptake of NA and 5-HT, increases virtually equipotently the extracellular levels of NA and 5-HT, confirming previous in vitro studies. In addition, the antagonism of 5-HT1A autoreceptors by (-)-pindolol potentiates the action of milnacipran on both NA and 5-HT systems, without modifying the ratio of these activities.

Adrenergic beta-Antagonists↗
PubMed1997

Autoradiographic localization of 5-HT1E and 5-HT1F binding sites in rat brain: effect of serotonergic lesioning.

5-carboxamidotryptamine (5-CT)-insensitive binding sites labelled by [3H]5-hydroxytryptamine (5-HT) in the presence of 100 nM 5-CT and 100 nM mesulergine, were examined by semi-quantitative autoradiography in rat brain. Under these conditions most of the labelled sites correspond to 5-HT1E and 5-HT1F sites. The 5-CT-insensitive binding is located mainly in cortical layer V, caudate-putamen, interpeduncular nucleus and claustrum. In cortex and caudate-putamen, a large proportion of 5-CT-insensitive sites is displaced by 250 nM sumatriptan and can be attributed to the presence of 5-HT1F receptors. A low, but significant, level of displacement by sumatriptan was observed in the choroid plexus. Lesions of serotonergic neurones by intracerebroventricular 5,7-dihydroxytryptamine injection does not significantly modify the densities of 5-HT1E or 5-HT1F binding sites. Our findings suggest that the 5-HT1F receptor has a limited distribution in rat brain, mainly located on non-serotonergic neurones.

Animals↗
PubMed1997

[Unusual facial clefts].

After briefly review facial morphogenesis, the authors define facial clefts, distinguishing primary clefts, secondary clefts, and residual clefts. They discuss the uncertainties surrounding the embryology and clinical features of palpebral colobomas. The various pathogenetic concepts are analysed: amniotic hypothesis, vascular hypothesis, fusion defect. The various classifications of rare facial clefts are reviewed, with particular emphasis on Tessier's classification and the so-called Milan classification. The general principles of surgical treatment are described together with the various skeletal and soft tissues procedures.

Craniofacial Abnormalities↗
PubMed1996

Effects of acute and repeated administration of citalopram on extracellular levels of serotonin in rat brain.

The effects of acute (2 days) and repeated (21 days) administration (50 mg/kg in the diet) of the selective serotonin (5-HT, 5-hydroxytryptamine) reuptake inhibitor, citalopram, on extracellular levels of 5-HT and their modulation by terminal autoreceptors in the hypothalamus of freely moving rats were compared in vivo by microdialysis. When studied without washout, extracellular levels of 5-HT were increased by both acute and repeated citalopram administration. In rats treated repeatedly, extracellular 5-HT levels were 43% (but not significantly) greater than in those treated acutely. Extracellular levels of 5-HT in control and citalopram-treated rats were similar when measured after 24 h washout. The enhancing effect of non-selective serotonergic autoreceptor antagonists, methiothepin (100 microM) or 1-(1-naphthyl)piperazine (NP) (10 microM), administered through the microdialysis probe, after 24 h washout, was similar in both control and chronically treated groups. These results suggest that repeated administration of citalopram followed by a washout of 24 h does not lead to desensitization of the terminal autoreceptor as measured in vivo in contrast to the effects we have shown previously in vitro. In rats treated chronically with citalopram without washout, methiothepin had a greater maximal effect on 5-HT outflow in comparison to rats receiving acute citalopram treatment. This finding suggests that a 5-HT autoreceptor antagonist or a combination of such a drug with a 5-HT uptake inhibitor would produce a greater increase of extracellular levels of 5-HT in hyposerotonergic states such as depression.

Animals↗
PubMed1996

Preclinical pharmacology of milnacipran.

Milnacipran (Ixel) is a new antidepressant which has been developed for its selective inhibition of both serotonin and noradrenaline reuptake and its lack of affinity for neurotransmitter receptors. It inhibits virtually equipotently the reuptake of serotonin and noradrenaline both in vitro and in vivo, as demonstrated by the antagonism of centrally acting monoamine displacers. It has no effect on dopamine reuptake. In addition, milnacipran has been shown by intracerebral microdialysis to increase the extracellular levels of both serotonin and noradrenaline after acute administration. Milnacipran is devoid of interactions at any known neurotransmitter receptor or ion channel. In particular, and unlike tricyclic antidepressants, it does not act at noradrenergic, muscarinic or histaminergic receptors. Contrary to tricyclic antidepressants, chronic administration of milnacipran does not modify beta-adrenoceptor binding or second messenger function. Milnacipran is active on various animal models of depression such as the forced swimming test in the mouse, learned helplessness in the rat and the olfactory bulbectomized rat model. This pharmacological profile, associated with an excellent bioavailability in man, was predicted to be that required for a powerful and well-tolerated antidepressant. Subsequent clinical development has shown this prediction to be well founded.

Adrenergic Uptake Inhibitors↗
PubMed1995

In vitro and in vivo activity of 1-(1-naphthyl)piperazine at terminal 5-HT autoreceptors in guinea-pig brain.

The effect of 1-(1-naphthyl)piperazine (NP) on the 5-HT terminal autoreceptor modulating 5-HT release was investigated in vitro and in vivo. In vitro 5-HT release was measured in slices of guinea-pig substantia nigra and hypothalamus prelabelled with 3H-5-HT, superfused with Krebs solution and depolarized electrically. NP, at 0.1 and 1 mumol/l, did not modify the calcium-dependent release of 3H-5-HT elicited by electrical stimulation using a frequency of 5 Hz, however at 0.1 mumol/l NP shifted to the right the inhibition curve of the non-selective autoreceptor agonist, 5-carboxamidotryptamine, in both regions. In hypothalamus when using lower frequencies (1 Hz or 0.2 Hz) or under pseudo-one-pulse stimulation, NP decreased the release of 3H-5-HT at 1 mumol/l. In vivo microdialysis was used to measure extracellular levels of endogenous 5-HT in the substantia nigra of freely moving guinea-pigs. The endogenous release of 5-HT was tetrodotoxin (TTX)-sensitive, indicating a neuronal origin of this efflux. NP, administered through the microdialysis probe (1-100 mumol/l), increased the levels of extracellular 5-HT in concentration-dependent and TTX-sensitive manner. These results suggest that in vitro NP acts as a 5-HT autoreceptor partial (ant)agonist in the substantia nigra and hypothalamus of guinea-pigs, and as a full antagonist in vivo. However, NP administered systemically at 10 mg/kg i.p., did not modify the levels of extracellular 5-HT in the substantia nigra. This lack of systemic effect of NP probably results from its interaction at other receptors that modify 5-HT neurotransmission.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Effect of mefenorex on 5-HT release: studies in vitro on rat hypothalamic slices and in vivo by microdialysis.

Mefenorex, used for 20 years as an anorexic drug, has not been studied so far with regard to its central mechanism of action, although its chemical structure suggests a serotonergic mechanism. In the present study, the effect of mefenorex on serotonin (5-HT) release was investigated both in vitro, on rat hypothalamic slices and in vivo, using microdialysis in the paraventricular (PVN)-ventromedian (VMH) hypothalamic area while mefenorex was applied locally by means of counterdialysis. In vitro, mefenorex increased the spontaneous release of 3H 5-HT from hypothalamic slices but not the electrically evoked release. This suggests a 5-HT releasing action of mefenorex not mediated through the terminal autoreceptor. The in vivo study confirmed the enhanced release and provided additional information. The delayed and modest increase of the 5-HT intracellular metabolite 5-HIAA may be indicative of an inhibition of reuptake. The dopaminergic system was also, but more modestly, activated by mefenorex. The increase in 5-HT release together with the inhibition of its reuptake may represent the main mechanism of action of mefenorex, and the secondary activation of the dopaminergic system may contribute in its anorexigenic effect at the level of the PVN-VMH area.

Amphetamines↗
PubMed1995

[The anatomy and the MRI anatomy of the interhemispheric cerebral commissures].

Correlation of myelin-stained or cryotomic sections of human brain with inversion-recovery MR images can display the cerebral commissures as white-matter tracts (in hypersignal on MRI), crossing the mid-line. MRI shows routinely in three orthogonal planes a) the corpus callosum stretched above the supra-tentorial ventricles, it's four portions (rostrum, genu, body and splenium) and connections with the Deep Grey Nuclei b) the fornix, intralimbic commissure joining anteriorly the mammillary bodies (through it's columns) to the alveus posteriorly and inferiorly (via it's two crura), arcing around the thalamus and lying over the hippocampus and the dentate gyrus as shown on the frontal sections c) the anterior commissure, white-matter tract connecting the two temporal lobes. In axial view, the anterior commissure has the shape of bicycle handlebars, coursing posteriorly, inferiorly and laterally behind the head of the caudate nucleus and passes into the lateral nucleus of the globus pallidus into the inferior and middle temporal gyri. Because the anterior commissure is easily recognisable in all planes, it's appears to be a important landmark for identification of the lateral and medial nuclei of the globus pallidus on axial and sagittal planes d) at least, the posterior commissure, anterior margin of the pineal region, closely related to the superior colliculi, acquire a major importance in the AC-PC line delineation becoming a reference landmark for stereotatical procedures.

Brain↗
PubMed1994

Autoradiographic characterization of binding sites for [3H]milnacipran, a new antidepressant drug, and their relationship to the serotonin transporter in rat brain.

Milnacipran is a new antidepressant drug and an equipotent inhibitor of the uptake of serotonin and noradrenaline. Quantitative autoradiography and radioligand binding studies were used to characterize recognition sites of [3H]milnacipran in rat brain. [3H]Milnacipran demonstrated saturable, reversible and nanomolar affinity binding. The binding was Na(+)-dependent, potently displaced by serotonin uptake inhibitors in all structures and moderately or weakly displaced by catecholamine uptake inhibitors (order of potency: paroxetine > fluoxetine > mazindol > desipramine > nomifensine > maprotiline). High density of recognition sites were found in structures dense in serotonergic innervation (raphe, basal ganglia, colliculi, cortex). The autoradiographic pattern of [3H]milnacipran recognition sites resembled that of [3H]paroxetine, but their distribution did not correlate well in some structures. Selective lesioning of serotonergic neurons by intracerebral injection of 5,7-dihydroxytryptamine caused a large decrease of [3H]milnacipran binding in various regions (septum, caudate, hippocampus, thalamus, ventral and dorsal hypothalamus), but in other structures, the [3H]milnacipran binding was partially affected (putamen) or even unchanged (amygdala, lateral hypothalamus). In contrast, lesion of noradrenergic neurons by intraperitoneal administration of [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine] did not affect the binding of [3H]milnacipran in any region. These results show that [3H]milnacipran mainly binds to the serotonin transporter and does not recognize the catecholamine transporters under the conditions used. In addition, [3H]milnacipran might also bind to other sites, serotonin transporter localized on non-serotonergic neurons or serotonergic neurons insensitive to 5,7-DHT neurotoxicity.

5,7-Dihydroxytryptamine↗
PubMed1994

Neuropharmacology of 5-hydroxytryptamine1B/D receptor ligands.

In spite of a lack of compounds acting selectively at the 5-hydroxytryptamine (5-HT)1B and 5-HT1D receptor subtypes, by cross-relating the available data, this review attempts to tentatively assign behavioural and other in vivo correlates of these receptor subtypes. In addition, a summary of data from microdialysis studies is included to develop an integrated view. Finally, a suggestion is made as to the possible pathophysiological consequences of 5-HT1D receptor dysfunction in man.

Animals↗
PubMed1994

Effect of milnacipran and desipramine on noradrenergic alpha 2-autoreceptor sensitivity.

1. The effects of chronic administration with milnacipran and desipramine on the noradrenergic alpha 2-autoreceptor sensitivity in the rat hypothalamus were compared. 2. Rats were administered, in their diet, milnacipran (50 mg/kg/day for 21 days, 24 h wash-out), desipramine (35 mg/kg/day for 21 days, 24 h wash out) or desipramine (14 mg/kg/day for 21 days, 41 h wash-out). Hypothalamic slices were incubated with [3H]noradrenaline, superfused and stimulated electrically. 3. Chronic administration with milnacipran did not modify basal or electrically induced release of [3H]noradrenaline, tissue incorporation of [3H]noradrenaline or the sensitivity of the alpha 2-autoreceptor assessed by the inhibition of the stimulation-evoked release of [3H]noradrenaline by the alpha 2-adrenoceptor agonist, guanabenz, in comparison to controls. After chronic desipramine (35 mg/kg), basal and evoked release of [3H]noradrenaline were increased, tissue incorporation of [3H]noradrenaline decreased and the inhibitory effect of guanabenz was diminished. At the lower dose (14 mg/kg), chronic desipramine increased only the evoked release of noradrenaline but did not modify the sensitivity of the alpha 2-autoreceptor. 4. Desipramine at 35 mg/kg remains in the tissue after 24 h wash out, causing a reduction of uptake and complicating the interpretation of the data.

Animals↗
PubMed1994

[Papilloma of the choroid plexus. Apropos of 11 cases].

The authors report 11 cases of choroid plexus papillomas in children operated on from 1979 until 1993. The age ranges from 2 months to 14 years old. The most frequent location occurred in the lateral ventricles (7 cases) followed by the locations in the third ventricle (3 cases) and the fourth ventricle (1 case). A complete resection was performed in all the cases. Hydrocephalus induced by the tumors was always present. An internal and permanent shunting procedure was carried out in the pre-operative period in 5 cases, in the post-operative course in 1 case. 3 cases underwent an external CSF shunting before surgery. This external CSF drainage has been taken out a few days after the surgical resection and no further permanent internal shunting was required in the long-term outcome. In 2 cases, no CSF drainage was performed either before or after surgery. Choroid plexus papillomas (CPP) require surgical management. The hypervascularisation of these tumors can give rise to important bleeding and generate surgical difficulties particularly in children under one year. The best way to remove these tumors would be to reach the arterial feeder(s) in first place, but it is not always possible. It's also difficult to forecast wether or nor the hydrocephalus will require further permanent CSF drainage, so we have chosen to carry on an external and transient CSF shunting.

Adolescent↗
PubMed1994

Present status of computerized tomography and angiography in the diagnosis of cerebral thrombophlebitis cavernous sinus thrombosis excluded.

In order to evaluate the contribution of computerized tomography (CT) to the diagnosis of cerebral thrombophlebitis, a series of 28 cases was reviewed and compared with data from the literature. In an examination carried out 4 to 5 days of its constitution the thrombus may be directly visualized as a spontaneous hyperdensity. This early but very transient sign, called "cord sign", can easily be overlooked, which explains why it was found in only 5 of our 28 cases and in 2% of the largest series of the literature. The thrombus thereafter becomes hypodense and can be intensified by peripheral contrast enhancement which produces the classical "delta sign". This sign is more frequent: 13/28 in our series and 16 to 30% in published cases. It is usually found in the superior sagittal sinus and must be distinguished from anatomical variations which are common at that level. These two direct signs acquire a greater value when associated with such indirect signs as diffuse or localized cerebral oedema (12 to 52%) and venous ischaemia (22 to 59%). Venous ischaemia is characterized by its strong bleeding potential (more than 50% of the cases) and by its usually favourable course; these two elements and its site differentiate it from arterial ischaemia. Finally, venous stasis is responsible, in 5 to 19% of the cases, for intense enhancement of the tentorium cerebelli; this sign is not specific but easy to evidence and of great value when associated with a direct sign. Dilatation of cortical veins, found in 4 of our 28 cases, also seems to be an interesting sign which, to our knowledge, has not yet been mentioned in the literature. Since in 3.6 to 26% of the cerebral thrombophlebitis the CT scan is normal, a negative CT examination does not rule out this disease, and in many cases the exploration must be rapidly completed by angiography or MRI. Because it is non-invasive and very sensitive to flows, MRI has become the key examination to assert the diagnosis. Angiography is now restricted to those cases where cases where MRI cannot be performed promptly or to certain, purely cortical thrombophlebitis which might pass unnoticed at MRI. When carried out and interpreted cautiously, angiography always shows the venous thrombosis, its exact size and its suppletive network. The results of this study show that MRI alone can diagnose cerebral thrombophlebitis in most patients, that CT well done and interpreted often provides useful but seldom sufficient indices, and that angiography should be reserved for difficult cases.

Cavernous Sinus↗
PubMed1994

[Pericranial sinus].

This study concerns four cases of sinus pericranii observed at the Neurological Department of Nancy. Sinus pericranii is a direct communication between the outer surface of the skull and the intracranial venous sinuses. It may be congenital, acquired or traumatic. This abnormality, usually located in the midline and often in the frontal region, is usually symptomless, but some patients complain of headache, nausea and vertigo. Sinus pericranii shows as a fluctuating non pulsatile mass of reddish or bluish colour, expanding when the patient bends his head down. Radiography usually shows one or several bone defects opposite the lesion found at CT bone window. On soft tissue window the mass is not calcified and usually enhanced by contrast injection. It is sometimes possible to visualize the vascular communication between the extracranial region and the underlying dural sinus. When visualization is blurred, or CT shows intracerebral abnormalities, MRI examination is required. Angiography with subtraction in venous phase (40 to 60 seconds after the injection), sometimes aided by films taken in head down position. It is of interest only in cases where CT and MRI have shown associated vascular abnormalities. Otherwise, direct injection of contrast medium into the malformation makes it possible to assert the diagnosis of sinus pericranii and to determine the flow rate within the malformation, which to some extent commands the the therapeutic technique. In patients with small and asymptomatic sinus pericranii absention is the rule. When the sinus is of moderate size, and the flow rate not rapid and when there is no significant communication with the cerebral veins, endovascular sclerosis may be advocated. In all other cases, surgical removal is recommended and is usually easy.

Angiography, Digital Subtraction↗
PubMed1993

Quantitative autoradiography of 5-HT1E binding sites in rodent brains: effect of lesion of serotonergic neurones.

Binding sites corresponding to 5-HT1E receptors were labelled in mouse, rat, and guinea-pig brains by using [3H]5-hydroxytryptamine ([3H]5-HT) in the presence of 5-carboxamidotryptamine (5-CT) (0.1 microM), and their distribution within the brain was studied by quantitative autoradiography. The results obtained with mouse brain show that 5-HT1E binding sites are particularly present in the cortex, caudate-putamen and claustrum, where they showed the highest density. Lower densities were measured in other regions. Saturation experiments showed that the affinity of [3H]5-HT for 5-HT1E binding sites (nanomolar range) was very similar in the different structures. The distribution of 5-HT1E binding sites was similar in rat and guinea-pig brains. In rat brain, selective lesioning of serotonergic fibres by intracerebroventricular injection of 5,7-dihydroxytryptamine (5,7-DHT), a specific 5-HT neurotoxin, did not affect the density of 5-HT1E binding, indicating that these receptors are mainly localized on non-serotonergic neurones.

5,7-Dihydroxytryptamine↗
PubMed1993

Does 5-carboxamidotryptamine-induced turning in guinea-pigs involve 5-HT1D autoreceptors?

Contralateral turning induced by unilateral injection of 5-carboxamidotryptamine (5-CT) into guinea-pig substantia nigra could result from unilaterally reduced inhibition of the dopaminergic pathway as a consequence of a decreased release of inhibitory 5-hydroxytryptamine (5-HT) through stimulation of 5-HT1D autoreceptors. This hypothesis was tested by administering 5-CT unilaterally to freely moving guinea pigs through a microdialysis probe, and simultaneously measuring extracellular 5-HT in the dialysate and rotation. A concentration of 250 mN 5-CT was required to produce significant turning. This also induced a massive increase in extracellular 5-HT, introduced as an impurity of the 5-CT. The presence of high concentrations of extracellular 5-HT makes it unlikely that 5-CT-induced rotation is mediated through decreased 5-HT release resulting from 5-HT1D autoreceptor stimulation.

Animals↗
PubMed1993

Neurobiological mechanisms involved in antidepressant therapies.

Selective serotonin reuptake inhibitors (SSRIs) are effective in alleviating the symptoms of depression. However, clinical improvement is only obtained after several weeks of treatment. SSRIs, when administered acutely to animals, have little effect on synaptic levels of serotonin. This suggests the existence of one or more regulatory mechanisms controlling serotonergic neurotransmission. The firing rate of dorsal raphe serotonergic neurons is under the control of somatodendritic 5-hydroxytryptamine 1A (5-HT1A) autoreceptors, the release of serotonin from nerve terminals is under the control of 5-HT autoreceptors (5-HT1B subtype in rodents, 5-HT1D in other species), whereas the control of the activity of tryptophan hydroxylase, the rate-limiting enzyme of serotonin synthesis, is complex, involving 5-HT1A but possibly other 5-HT receptors including the 5-HT1B/D subtype. During prolonged administration with a SSRI, these three feedback systems become desensitized and their regulatory effects on serotonergic neurotransmission are weakened or lost. This has the effect of allowing the synaptic levels of serotonin to rise with a consequently increased stimulation of one or more types of postsynaptic 5-HT receptor. Thus, it is only after prolonged administration that the pharmacological activity of SSRI is fully expressed in terms of synaptic serotonin levels. This may explain the latency of antidepressant action seen with these drugs in humans. Various other classes of antidepressant therapies (tricyclic antidepressants and monoamine oxidase inhibitor drugs, electroconvulsive therapy) have long-term effects on one or more of the feedback mechanisms such that an increase in synaptic concentrations of serotonin may be a common mechanism of many antidepressant therapies.

Animals↗