Biomedical subjects

M Jouvet

Publications and source records attributed to M Jouvet.

At least 91 records · Page 5Linked to original sources

PubMed1993

Anatomical distribution of prolactin-like immunoreactivity in the rat brain.

The present study examines prolactin PRL-like immunoreactivity (PRL-LIR) in the rat central nervous system and describes the distribution of labeled perikarya and fibers using a specific antiserum to ovine PRL. This antiserum does not cross-react with molecules of the pro-opiomelanocortin (POMC) family and recognizes rat PRL. PRL-LIR cell bodies are found exclusively in the lateral hypothalamic area surrounding the fornix, especially dorsolateral to it. No labeled cells are detectable in any other part of the brain, including the arcuate nucleus. Labeled fibers are dispersed in almost all parts of the brain. Dense plexuses are observed in the hypothalamus, midline thalamus nuclei, bed nucleus of stria terminalis, raphe dorsalis, and locus coeruleus. There is no apparent decrease in the number of PRL-LIR cell bodies and fibers in hypoprolactinemic mutant rats or after hypophysectomy, suggesting that central PRL is synthesized in such hypothalamic neurons. Comparison of PRL and alpha-melanocyte-stimulating hormone immunostainings provides evidence that the PRL network is independent of those of POMC and melanin-concentrating hormone. The present results support the hypothesis of two independent PRL systems: one peripheral (pituitary gland) and the other cerebral. Concerning the functional role of brain PRL, its widespread projections suggest that PRL is involved in multiple regulations. The presence of PRL-LIR in brain areas involved in sleep-wake control is a strong argument for its role in such a regulation.

Animals↗

PubMed1993

Glycine-immunoreactive neurones in the cat brain stem reticular formation.

Using a specific glycine antiserum, we determined the localization of glycinergic neurones and fibres in the cat brain stem reticular formation. We visualized a large number of glycine-immunoreactive cell bodies and fibres in the medullary reticularis gigantocellularis, magnocellularis, paragigantocellularis lateralis and parvocellularis nuclei. The pontis oralis and caudalis and the raphe magnus nuclei also contained a large number of glycine-immunoreactive fibres but fewer neurones. Using a double staining method, we further observed glycine-immunoreactive boutons over (1) noradrenergic neurones in the locus coeruleus complex and the ventrolateral and dorsomedial medulla, (2) serotoninergic neurones in and outside the raphe nuclei and (3) cholinergic neurones in the pedunculopontine and laterodorsal tegmental nuclei. These results suggest that glycinergic neurones in the reticular formation may be involved in aspects of paradoxical sleep, including the general muscle atonia seen during this sleep state.

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PubMed1992

Dopaminergic neurons in the cat dorsal motor nucleus of the vagus, demonstrated by dopamine, AADC and TH immunohistochemistry.

In the rostral part of the dorsal motor nucleus of the vagus of the cat, neurons do not contain histochemically detectable catecholamines, even though many perikarya contain both intense aromatic L-amino acid decarboxylase (AADC) immunoreactivity and strong monoamine oxidase enzymatic activity. Similarly located perikarya have distinct immunoreactivities to tyrosine hydroxylase (TH) and dopamine after treatment with colchicine. Since inhibition of monoamine oxidase fails to reveal dopamine in these cells, its absence in non-colchicine-treated animals cannot be due to rapid deamination. It appears that dopamine is synthesized by TH and AADC in dorsal motor vagal cells and is then rapidly transported from the perikarya.

Animals↗

PubMed1992

Role of catecholamines in the modafinil and amphetamine induced wakefulness, a comparative pharmacological study in the cat.

Seventeen adult cats were chronically implanted with electrodes for polygraphic recordings in order to assess the role of catecholamines in the arousal effects of oral administrations of modafinil, a presumed noradrenergic agonist, and amphetamine, a well-known catecholamine-releasing agent. Whereas both modafinil (1, 2.5 and 5 mg/kg) and amphetamine (0.25, 0.5 and 1 mg/kg) caused a significant and dose-dependent increase in wakefulness and brain temperature, amphetamine, but not modafinil, elicited marked signs of behavioral excitation. Pretreatments with alpha-methyl-DL-p-tyrosine methyl ester (50 mg/kg, i.p.), an inhibitor of catecholamine synthesis, almost completely prevented the effects of amphetamine (0.25 and 1 mg/kg), but only slightly reduced the duration of the waking effect of modafinil (2.5 and 5 mg/kg). Pretreatments with phentolamine (10 mg/kg, i.p.), prazosin (1.5 mg/kg, per os) and propranolol (5 mg/kg, i.p.), an alpha-, alpha 1- and beta-receptor antagonist, respectively, attenuated significantly the arousal effect of modafinil (1 mg/kg, the same as below) but not of amphetamine (0.25 mg/kg, the same as below). Intraperitoneal injections of haloperidol (0.5 mg/kg), a dopamine-receptor antagonist, blocked significantly the arousal of amphetamine but not of modafinil. The effects of both modafinil and amphetamine were enhanced by a pretreatment with yohimbine (1 mg/kg, i.p.), an alpha 2-receptor antagonist. These results suggest that the arousal effect of modafinil does not depend on the availability of the endogenous catecholamines but results from an enhancement of alpha 1- and beta-receptor activity and that the waking and behavioral effects of amphetamine may be mainly due to an increase in dopamine release.

Amphetamine↗

PubMed1992

Effects of chronic atropine administration on regional vasoactive intestinal polypeptide concentrations in rat brain.

We studied the effects of 14 days' treatment with atropine sulfate (10 or 20 mg/kg per day) or atropine methyl bromide (20 mg/kg per day) on the concentration of vasoactive intestinal polypeptide like-immunoreactivity (VIP-LI) in the rat brain. VIP-LI in the anterior pituitary as well as brain areas dissected from treated and control rats was measured by radioimmunoassay. VIP-LI in the hypothalamus, and especially in the suprachiasmatic nucleus, was not affected by chronic atropine sulfate administration. Conversely, the same treatment induced a decrease in VIP-LI in the cerebral cortex, dorsal raphe, locus coeruleus, ventrolateral and dorsolateral medulla. In these structures, the decrease in VIP-LI was probably due to muscarinic receptor blockade in the central nervous system rather than in the peripheral nervous system since variations in VIP-LI were not observed after atropine methyl bromide treatment. These findings suggest the existence of a muscarinic control of VIP-LI in discrete brain areas of the rat and particularly in caudal brainstem structures.

Animals↗

PubMed1992

Distribution of enkephalin and its relation to serotonin in cat and monkey spinal cord and brain stem.

The distribution of enkephalin (ENK)-like immunoreactivity (LI) in spinal cord and medulla oblongata of cat and gray monkey (Macaca fascicularis) was studied by use of immunofluorescence and peroxidase antiperoxidase (PAP) techniques. Possible coexistence between ENK- and 5-hydroxytryptamine (5-HT)-LI was also analyzed with double labeling immunofluorescence. Furthermore, in situ hybridization was used to demonstrate cell bodies in the brain stem expressing mRNA encoding for ENK. ENK-immunoreactive (IR) axonal varicosities and fibers were demonstrated throughout the spinal cord gray matter, with the highest density in the superficial dorsal horn, the area around the central canal, the intermediolateral cell column, the sacral parasympathetic nucleus, and in Onuf's nucleus. In the monkey ventral horn, ENK-IR varicose fibers could in some cases be demonstrated in very close apposition to cell bodies. A low degree of co-localization between ENK- and 5-HT-LI was seen in the spinal cord of both species. Still, fibers containing both compounds could as a rule be demonstrated in every section studied. The highest degree of coexistence was encountered in the motor nucleus of the ventral horn. Six weeks after a low thoracic spinal cord transection a decreased staining for ENK-LI was demonstrated in the ventral horn motor nucleus, whereas other parts of the spinal cord appeared unaffected. In the brain stem of cats after colchicine treatment, ENK-LI was found in a majority of the 5-HT-IR cell bodies in the raphe nuclei (nucleus raphe magnus, pallidus and obscurus) and in the lateral reticular nucleus (rostroventrolateral reticular nucleus). In cat not pretreated with colchicine, a few weakly stained ENK-IR cell bodies could be found in the midline raphe nuclei and in the lateral reticular nucleus with the PAP technique. In the monkey brain stem without colchicine treatment, using the PAP technique, heavily stained ENK-IR cell bodies could be seen in the lateral reticular nucleus whereas, as in the cat, only a few, weakly stained ENK-IR cell bodies could be seen in the midline raphe nuclei. Using in situ hybridization technique, ENK mRNA expressing cells were demonstrated in the lateral reticular nucleus while no convincing mRNA signal could be found over cell bodies in the raphe nuclei. It is concluded that part of the ENKergic innervation of the cord in both species derives from supraspinal or suprasegmental levels.(ABSTRACT TRUNCATED AT 400 WORDS)

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PubMed1992

Effect of paradoxical sleep deprivation on vasoactive intestinal peptide-like immunoreactivity in discrete brain areas and anterior pituitary of the rat.

To determine whether vasoactive intestinal peptide (VIP) is involved in paradoxical sleep (PS) homeostasis, VIP-like immunoreactivity (VIP-LI) of discrete brain areas was determined by radioimmunoassay after 24 and 48 h of PS deprivation by the watertank technique followed or not by 5 h of sleep rebound. This study was carried out with an environmental control (placed in dry watertank: DWC) and a nonstressed control. Such PS deprivation induced a decrease of VIP content in PS-deprived rats restricted to cortex and anterior pituitary. In the cortex, the decrease in VIP-LI was of the same magnitude after 24 and 48 h of PS deprivation and VIP-LI was normal by 5 h of sleep rebound; as such a decrease was also observed after 48 h in DWC, it could be due to the stress related to the experiment rather than lack of sleep. In the anterior pituitary, the decrease was related to the duration of deprivation with a greater decrease in VIP-LI after 48 than after 24 h of PS deprivation and specifically related to PS deprivation since it was not observed in DWC rats. After 5 h of sleep rebound, recovery of VIP-LI was total in the 24-h experiment and partial in the 48-h one. In all eight other structures studied, VIP was unchanged after experimentation. These results strongly suggest that VIP is not involved in PS homeostasis but as indicated by other experiments more probably in circadian organization of sleep.

Animals↗

PubMed1992

Axonal and somato-dendritic modalities of serotonin release: their involvement in sleep preparation, triggering and maintenance.

That serotonin (5-HT) plays a determinant role in sleep was first suggested by the well-known PCPA-5HTP (p.chlorophenylalanine-5-hydroxytryptophan) paradigm. This involvement, however, is paradoxical since localized cooling of the nucleus raphe dorsalis (n.RD) is sleep inducing, and unitary activity of 5-HT neurons decreases during slow wave sleep (SWS) and paradoxical sleep (PS). Furthermore, on the basis of voltammetric 5-hydroxyindole (5-OHles) measurements, it appears that 5-HT could be released throughout the sleep/wake cycle according to two different modalities: by the axonal nerve endings during the waking state (W) and by the dendrites and/or the soma during sleep. The axonal release of 5-HT might participate in sleep preparation by stimulating the synthesis of hypnogenic factors within target structures like the basal hypothalamus (BH). When such a release is increased by an immobilization stress (IS) or electrical stimulation of the n.RD, a sleep rebound is induced. The somato-dendritic release of 5-HT might be primarily responsible through an auto-inhibitory process for the decrease and abolition of the 5-HT neuronal unitary activity as well as for the reduction of the axonal release of 5-HT; both phenomena being constantly observed during sleep. Finally, the hypnogenic factors might initiate and maintain sleep by influencing the n.RD sleep gating mechanisms either through the somato-dendritic release of 5-HT, or directly.

Journal Article↗

PubMed1992

Paradoxical sleep deprivation increases glutamine synthetase in rat brain.

The modifications of glutamine synthetase (GS) level, an enzyme mainly located in astrocytes, were investigated in rat after paradoxical sleep deprivation and during recovery. An immunotitration method was used to evaluate the relative level of GS in brain tissue. At the end of a 24 hrs. paradoxical sleep deprivation, a significant increase in GS level was observed both in the frontoparietal cortex and the locus coeruleus area. 4 hrs. later, during recovery, the GS level returned to control level in the cortex but was lower in the locus coeruleus area.

Animals↗

PubMed1992

[Demonstration of prolactin messenger RNA after amplification in the brain in rats].

By means of immunocytochemistry, a central neuronal network containing a prolactin-like substance has been described in the rat. In order to demonstrate the synthesis of this peptide in these cells, we examined the presence of prolactin messenger RNA (PRL mRNA) in several brain samples including the pituitary gland. Amplification of the PRL mRNA was performed by the polymerase chain reaction technique, followed by southern blotting and hybridization with a specific oligonucleotide. Results showed the presence of the expected cDNA (468 bp) in the hypothalamus. Another cDNA with a lower molecular weight was also observed.

Animals↗

PubMed1991

Effects induced by the electrical stimulation of the nucleus raphe dorsalis upon hypothalamic release of 5-hydroxyindole compounds and sleep parameters in the rat.

Electrical stimulation (30 min; pulse 0.5 ms, 150 microA, 20 Hz) of the antero-dorsal part of the nucleus raphe dorsalis (n.RD) induces in the basal hypothalamus (n. arcuate and surrounding areas) a large axonal release of 5-hydroxyindole compounds (5-OHLes; about +300%) measured by means of voltammetric technique. During such a release, evidence for a direct detection of serotonin (5-HT) is reported. The above stimulation induces also marked aversive behaviors together with prolonged polygraphic arousal. Three hours later, a significant paradoxical sleep (PS) rebound occurs. Both the 5-OHLes release and the PS rebound observed after n.RD stimulation are suppressed by a p-chlorophenylalanine (PCPA) pretreatment of the animals. The 5-HT-hypnogenic factor dependence of the PS rebound observed after n.RD stimulation is discussed.

Animals↗

PubMed1991

Distribution of the pro-opiomelanocortin-immunoreactive axons in relation to the serotoninergic neurons in the dorsal raphe nucleus of the rat.

The anatomical relationships between pro-opiomelanocortin-containing axons and serotonin neurons in the nucleus raphe dorsalis (NRD) of the rat were examined at the light microscope level with antibodies against CLIP (corticotropin-like intermediate lobe peptide), alpha-MSH (alpha-melanocyte-stimulating hormone) and serotonin. Sequential double labeling was performed with either immunofluorescence or peroxidase-antiperoxidase techniques. It was observed that the network of POMC-immunoreactive axons displayed a gradient of decreasing density from rostral to caudal levels and from dorsal to ventral parts or the NRD. The examples of close proximity between immunoreactive axons and serotonin cell bodies or dendrites were rather scarce. On the whole, the immunoreactive fibers seemed to run quasi-independently of the serotonin neurons.

Adrenocorticotropic Hormone↗

PubMed1991

Carbachol microinjections in the mediodorsal pontine tegmentum are unable to induce paradoxical sleep after caudal pontine and prebulbar transections in the cat.

In 7 cats, total transections of the brainstem at the caudal pontine or the prebulbar level led to preparations which presented neither behavioral nor electrophysiological signs of paradoxical sleep (PS) throughout their survival periods (17-30 days). Carbachol microinjections in the mediodorsal pontine tegmentum (MDPT), which induced PS in the intact cat, were no longer able to induce it in the transected animals. Rapid eye movement (REM) and pontogeniculo-occipital (PGO)-like bursts were evoked by carbachol microinjections in the pontine magnocellular tegmental field (FTM) of cats transected at the prebulbar level, as in the intact cat. Only REM bursts were obtained by the same injections in caudal pontine transected cats. It is concluded that (1) the pons is insufficient to generate PS; (2) complex reciprocal interactions with the medulla are necessary for the generation of this state of sleep; and (3) the production of long REM and PGO bursts is controlled by the caudal pontine tegmentum.

Animals↗

PubMed1991

Anatomical and electrophysiological evidence for a glycinergic inhibitory innervation of the rat locus coeruleus.

Using a highly specific antiserum to glycine and a very sensitive immunohistochemical technique with streptavidin-horseradish peroxidase, we visualized for the first time a dense plexus of glycine varicose fibers in the locus ceruleus (LC) of the rat. We further demonstrated that iontophoretically applied glycine inhibits the spontaneous LC noradrenergic cell discharge and that this inhibition is blocked by co-iontophoresis of strychnine. These anatomical and electrophysiological results indicate that the rat locus ceruleus receives an inhibitory glycinergic input.

Animals↗

PubMed1991

Immunohistochemical evidence for the presence of type B monoamine oxidase in histamine-containing neurons in the posterior hypothalamus of cats.

Using a double immunostaining method, we demonstrated that type B monoamine oxidase (MAO-B) immunoreactivity was present in virtually all histamine (HA)-immunoreactive neurons in the posterior hypothalamus of the cat. Not all MAO-B-positive neurons, however, displayed HA immunoreactivity: a minor group of neurons immunoreactive for MAO-B alone was observed in the area dorsolateral to the caudal arcuate nucleus. The results suggest that the degradation of tele-methylhistamine might occur within the intraneuronal structures of histaminergic neurons.

Animals↗

PubMed1991

Immobilisation stress induces a paradoxical sleep rebound in rat.

An immobilisation stress (IS) of 2 h applied to rats at the beginning of the dark period (12 h), i.e. when the animals are more active, induces during the 10 consecutive h a significant rebound (+92%) of paradoxical sleep (PS) while slow-wave sleep state (SWS) is poorly affected. Two h of sleep deprivation, also applied at the beginning of the dark period and realized either by the platform technique or by maintaining the animals awake with gentle handling, do not affect significantly subsequent SWS and PS. Finally, when repetitive IS are inflicted to the animals (one IS of 2 h every 3 days) an attenuation of the PS rebound is observed. These data suggest that a qualitative aspect of the waking state as in an intense stressful situation might be the source of a hormonal process inducing a PS excess.

Animals↗

PubMed1991

Effect of modafinil and amphetamine on the rat catecholaminergic neuron activity.

We have studied the effect of modafinil and amphetamine, two waking drugs, on the electrical activity of central dopaminergic and noradrenergic neurons in the rat. Modafinil (128 mg/kg, i.p.) was unable to modify the firing pattern of these neurons, while amphetamine (2 or 5 mg/kg, i.p.) consistently inhibited their activity. A pretreatment with modafinil did not change thereafter the effect of amphetamine. Contrary to amphetamine, the waking effect of modafinil does not seem to be mediated by the catecholaminergic neuron activity per se.

Animals↗

PubMed1991

Neurotoxic lesion of the mesencephalic reticular formation and/or the posterior hypothalamus does not alter waking in the cat.

In order to re-evaluate the role of two putative waking systems, we injected a neural cell body toxin, ibotenic acid (IA) (45 micrograms/microliters), into the mesencephalic reticular formation (MRF) and/or the posterior hypothalamus (PH). On the one hand, when the cell body destruction was only restricted to the MRF, the IA microinjection was followed by a temporary high voltage and slow neocortical electroencephalogram (EEG) during the first 24 postoperative hours and by a subsequent long term increase in waking which lasted 8-12 h. After the first postoperative day, there were no motor disturbances, no aphagia nor adypsia, no alteration of cortical activation and no modification of thermoregulation or of the sleep-waking cycle. On the other hand, the IA microinjection into the PH induced a hypothermia during the first postoperative night and a dramatic transient hypersomnia immediately after the disappearance of the anesthesia (14-24 h after the IA injection). On the third day, all cats recovered control level of paradoxical sleep (PS), slow wave sleep (SWS) and cerebral temperature. They presented normal motor behavior but they were not able to eat by themselves during the first postoperative week. Finally, when the lesions of the MRF and the PH were realized in one single operation, the cats were first motionless in a comatose state for 2-3 days. This state was accompanied by a transitory hypothermia and the suppression of a spontaneous or evoked cortical low voltage fast activity. However, from the 2nd postoperative week, both behavioral and EEG waking re-occurred. By contrast, the two successive operations (MRF followed by PH) did not induce a comatose state. We did not observe any deficit in motor behavior, and the sleep-waking cycle was quite normal as from the second postlesion day. In the MRF-PH-lesioned cats, the injection of alpha-methyl-p-tyrosine (150 mg/kg) induced a large decrease in waking and a moderate increase in PS. In the MRF-lesioned cats, IA produced a large area of cell body loss, centered in the MRF, that extended from levels A2 to A6 of stereotaxic planes and sometimes encroached upon the red nucleus and the substantia nigra. In the PH-lesioned cats, the histological analysis revealed a great loss of cell bodies in the PH extended from levels A8 to A12.5. The damage included the lateral and posterior hypothalamic areas and sometimes the tuberomamillary nucleus. In MRF- and PH-lesioned cats, the cell body loss extended from levels A2 to A12.5.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗