Biomedical subjects

R Cespuglio

Publications and source records attributed to R Cespuglio.

At least 37 records · Page 2Linked to original sources

PubMed1995

Sleep permissive components within the dorsal raphe nucleus in the rat.

Two peptides known for their hypnogenic properties, CLIP (corticotropin-like intermediate lobe peptide or ACTH 18-39) or VIP (vasoactive intestinal polypeptide), were injected locally into the nucleus raphe dorsalis (nRD) of rats pretreated with p-chlorophenylalanine (PCPA). During the dark period, the PCPA insomnia was primarily associated with a reduction in paradoxical sleep (PS), whereas both slow wave sleep (SWS) and PS were decreased during the light period. Immunohistochemistry of serotonin in PCPA-pretreated animals indicated a clear disappearance of 5-HT fibers in the basal hypothalamus and the nRD as compared to control animals. Local injections of CLIP or VIP in the nRD restored PS and SWS. The positive injection sites corresponded to the anatomical distribution of either CLIP or VIP fibers, i.e., the entire nRD for VIP and the antero-dorsal part of this nucleus for CLIP. The sleep effects obtained in PCPA-pretreated rats involve a non-5-HT sleep permissive component within the nRD upon which these injected peptides act.

Adrenocorticotropic Hormone↗

PubMed1995

Induction of muricidal behavior by ACTH or adrenalectomy in young male Wistar rats.

ACTH administered IP induces a muricidal behavior in 52% of male Wistar rats that do not express it before; such behavior is also observed spontaneously in 68% of adrenalectomized animals. This change in behavior is characterized by an exceptionally long duration (several months in some animals), and by its prevention by previous or substitutive treatments with dexamethasone. Data obtained using hypophysectomized or adrenalectomized animals with or without ACTH treatments suggest that the muricidal-inducing effect of ACTH might have, at least partially, a central origin.

Adrenal Glands↗

PubMed1995

Evidence for a sleep-promoting influence of stress.

In the present review the data supporting the existence at the central level of a stress-sleep relation are reported and discussed. An immobilization stress of 1 or 2 hour(s) is accompanied by a marked polygraphic waking and followed by a significant sleep rebound concerning mainly paradoxical sleep (PS). During the restraint, an important release of 5-hydroxyindoles [5-OHles, a good index of serotonin (5-HT) release] occurs in the basal hypothalamus (BH). This release, produced by the nerve endings originating from the nucleus raphe dorsalis (nRD), might secondarily influence the release and/or the synthesis of hypnogenic substances directly involved in the sleep rebound production. Corticotropin-like intermediate lobe peptide (CLIP, or ACTH18-39) is a peptide possessing hypnogenic properties and derived from proopiomelanocortin (POMC) whose perikarya are contained within the BH (arcuate nucleus). The POMC nerve endings impinge on the nucleus raphe dorsalis, a structure containing sleep permissive components upon which CLIP acts to trigger sleep. It remains to be defined how the activity of the neuronal loop described above is impaired under chronic stress conditions.

Acute-Phase Reaction↗

PubMed1995

In vivo electrochemical monitoring of serotonin in spinal dorsal horn with Nafion-coated multi-carbon fiber electrodes.

Biosensors sensitive for in vivo monitoring of serotonin (5-HT) in the CNS by differential normal pulse voltammetry were constructed by coating treated multicarbon fiber electrodes (mCFEs) with Nafion (N-mCFE). In vitro sensitivities of mCFE and N-mCFE were compared in solutions ranging from 5 nM to 20 microM of uric acid (UA), 5-hydroxyindoleacetic acid (5-HIAA), and 5-HT. The mCFEs were three to seven times less sensitive for 5-HIAA or UA than for 5-HT. Nafion treatment dramatically decreased sensitivity for 5-HIAA and UA of N-mCFEs (approximately 10(3) times), whereas it remained in the nanomolar range for 5-HT. In vivo, in the dorsal horn of the lumbar spinal cord of anesthetized rats, the monoamine oxidase inhibitor clorgyline (10 mg/kg i.p.) produced a reduction (55 +/- 3% at 180 min) of peak 3 of oxidation current (characteristic of 5-hydroxyindoles) monitored with mCFEs, but with N-mCFEs (in this latter case the peak was termed 3N) peak 3N increased to 135 +/- 5% at 180 min. The 5-HT release-inducer p-chloroamphetamine (PCA; 6 mg/kg i.p.) induced a slight (12 +/- 3% at 150 min) decrease in peak 3 measured with mCFEs, whereas with N-mCFEs PCA induced a rapid increase of peak 3N (137 +/- 6% at 90 min). The xanthine oxidase inhibitor allopurinol (10 mg/kg i.p.) produced a decrease (30 +/- 3% at 180 min) in peak 3 (mCFEs), but peak 3N (N-mCFEs) was not affected (106% at 180 min). After pretreatment with allopurinol, PCA also produced an increase (135 +/- 6% at 90 min) in peak 3N.(ABSTRACT TRUNCATED AT 250 WORDS)

Allopurinol↗

PubMed1994

Immunocytochemical study of the CLIP/ACTH-immunoreactive nerve fibres in the dorsal raphe nucleus of the rat.

The injection of corticotrophin-like intermediate lobe peptide (CLIP) in the lateral ventricle or the dorsal raphe nucleus (DRN) of the rat is followed by a significant increase in the amount of paradoxical sleep. In the DRN, CLIP would act through a somatic and/or dendritic release of serotonin. To establish the anatomical basis of these effects, the nerve fibres immunoreactive for CLIP/ACTH were labelled and their fine anatomical relationships with the neuronal elements of the DRN were studied at the ultrastructural level. Half of the profiles of labelled varicosities were 'free' in the neuropile, the other half was in close contact with dendrites, either shafts or spines. It was interesting to note that few contacts with dendritic shafts were under the form of a synapse, whereas a large number of the contacts with spines were synaptic. The chemical nature of these dendritic targets remains to be determined but preliminary results indicate that they are partly serotoninergic.

Adrenocorticotropic Hormone↗

PubMed1994

Is the nucleus raphe dorsalis a target for the peptides possessing hypnogenic properties?

Several peptides exhibiting hypnogenic properties when administered i.p., i.v. or i.c.v. are now known. No data, however, are available concerning their targets in the brain. In the present work we hypothesize that the nucleus raphe dorsalis (nRD) may be one such target since it contains 2 sleep permissive components that must be influenced for sleep to occur. One of these components is serotoninergic in nature and gates the occurrence of ponto-geniculo-occipital (PGO) waves. The other, of unknown nature, influences tonic sleep phenomena. For hypnogenic peptides, a putative mechanism permitting the triggering and maintenance of sleep might consist of influencing both the above components. In the present work, 3 hypnogenic substances, CLIP (corticotropin-Like intermediate lobe peptide), VIP (vasoactive intestinal polypeptide) and DSIP (delta sleep inducing peptide), were injected into the nRD in order to determine whether these compounds still induce sleep by local administration. To verify that such local injections do not spread outside the nRD, radiolabelled CLIP and VIP were also injected. Autoradiograms obtained with either labeled CLIP or VIP indicate that these compounds, injected in a 0.2 microliter volume, do not spread outside the nRD. The sleep data obtained confirm that CLIP, at a dose of 10 ng, induces an increase in duration of paradoxical sleep (PS); this effect is observed only for injection sites located in the dorsolateral part of the nRD, an area where CLIP immunoreactive (IR) fibers are present. VIP, at a dose of 100 ng, also increases PS duration, whereas at 10 ng, only slow wave sleep duration is increased. In this case, the positive injection sites are scattered throughout the entire nRD as are the VIP-IR fibers. With DSIP, no sleep effect was found whatever the dose used or the site injected; in the same manner, no DSIP-IR fibers have been located in this structure. These data suggest that the nRD is a target for the expression of the hypnogenic properties of CLIP and VIP, but not for DSIP. The nature of the possible mechanisms permitting such expression are discussed.

Adrenocorticotropic Hormone↗

PubMed1994

Effects of an acute immobilization stress upon proopiomelanocortin (POMC) mRNA levels in the mediobasal hypothalamus: a quantitative in situ hybridization study.

The aim of this study was to examine by quantitative in situ hybridization the effects of an acute stress on the expression of the POMC gene in the mediobasal hypothalamus (MBH) of the rat. In control animals, the highest levels of POMC mRNA were observed in the posterior periventricular region of the MBH. Lower levels were found in the anterior and posterior arcuate nucleus. At the end of a one hour immobilization, a small decrease (-8%) was observed in the periventricular region only. Four hours after the end of immobilization, increases in POMC mRNA levels were detected in the anterior part (7%), in the posterior part (25%) and in the periventricular region (13%) of the MBH. These results suggest that MBH POMC-derived peptides might be an important component in the central response to stress.

Analysis of Variance↗

PubMed1993

High sensitivity measurement of brain catechols and indoles in vivo using electrochemically treated carbon-fiber electrodes.

The combination of electrochemically treated carbon-fiber electrodes with DPV, DNPV or DPA represents a wide range of possibilities. As shown in this review, the choice of treatment and measurement technique depends on the purpose. As regards in vivo monitoring of 5-HIAA or DOPAC from very small brain nuclei, electrochemically treated carbon-fiber electrodes appear very potent and inexpensive. The main limitation of the established electrochemical techniques, including those discussed here, is that the unequivocal measurement of the basal extracellular neurotransmitter level cannot be achieved unless animals are treated with pargyline. On the other hand, this monitoring is feasible with in vivo dialysis. Therefore, electrochemical techniques, on the one hand, and in vivo dialysis, on the other hand, present different advantages. The former are much more potent than the latter in two respects. First, due to the much smaller size of the sensor, electrochemical techniques are more suitable for studying small brain nuclei. Second, since electrochemical techniques exhibit a better temporal resolution, they are recommended for investigating the relationship between impulse flow and neurotransmitter release. However, when high anatomical or temporal resolution is not required, in vivo dialysis is more suitable for recording the basal monoamine release.

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

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

Detection of the release of 5-hydroxyindole compounds in the hypothalamus and the n. raphe dorsalis throughout the sleep-waking cycle and during stressful situations in the rat: a polygraphic and voltammetric approach.

In the present work, voltammetric method combined with polygraphic recordings were used in animals under long-term chronic conditions; the extracellular concentrations of 5-hydroxyindole compounds (5-OHles) and in particular 5-hydroxyindoleacetic acid (5-HIAA) were measured in the hypothalamus and in the nucleus Raphe Dorsalis (n.RD). The hypothesis that extracellular detection of 5-HIAA, in animals under physiological conditions, might reflect serotonin (5-HT) release is suggested by the following observations: serotoninergic neurons are reported to contain only monoamine oxidase type B (MAO-B);--an inhibitor of such an enzyme, MDL 72145 (1 mg/kg), fails to decrease the extracellular 5-HIAA peak 3 height:--MAO type A is contained in non-5-HT cells or neurons;--only the inhibitor of this last type of enzyme (Clorgyline 2.5 mg/kg) induces a complete disappearance of the voltammetric signal. The 5-HIAA measured in the extracellular space thus comes from the 5-HT released and metabolized outside the 5-HT neurons. Throughout the sleep-waking cycle, 5-OHles release occurs following two different modes: 1--during sleep, in the vicinity of the 5-HT cellular bodies in the n.RD; this release might come from dendrites and be responsible for the 5-HT neuronal inhibition occurring during sleep; 2--during waking, at the level of the axonal nerve endings impinging on the hypothalamus; this release might be related to the synthesis of "hypnogenic factors". Finally, we have observed that in the hypothalamus, 30 min. of immobilization-stress (IS) induces a larger increase of the voltammetric signal (+80%) than a painful stimulation of the same duration (+30%); the possible link between the 5-OHles release occurring in this area during an IS and the subsequent paradoxical sleep rebound is discussed.

Allylamine↗

PubMed1990

Time-course variations induced by pargyline on the 5-hydroxyindole compounds measured in the nucleus raphe dorsalis and in blood: a voltammetric and HPLC approach in the rat.

Ninety min after pargyline (Pargy, 75 mg/kg) injection, the +300 mV voltammetric signal, measured in the nucleus raphe dorsalis (nRD) of freely moving rats, disappeared completely. This effect was also followed (2-7 h post-injection) by the reappearance of a peak (post-Pargy-peak) at the same +300 mV potential. The height of this post-Pargy signal was still decreased by Pargy (30 or 75 mg/kg). Endogenous 5-hydroxyindoleacetic acid (5-HIAA) contents, measured with HPLC in the nRD of Pargy-treated rats, exhibited analogous variations. Inhibition of monoamine oxidases by Pargy seems thus to be effective in blocking 5-HIAA production over only 2 h. The 15-fold increase of 5-HT endogenous content in the nRD (3 h after injection) was not reflected in the voltammetric extracellular measurements performed 90 min to 7 h after Pargy injection; this increase is suspected to be mainly intracellular.

Animals↗

PubMed1990

Circadian rest-activity rhythms in the anophthalmic, monocular and binocular ZRDCT/An mice. Retinal and serotoninergic (raphe) influences.

In the present study, two strains of mice were used: the control C57 Black/6 and the experimental ZRDCT/An, composed of anophthalmic (AN), monocular (mono) and binocular (bi) animals. The circadian rest-activity rhythms of these mice, submitted to a 12 h/12 h light/dark (L/D) cycle, present different characteristics. In C57 Black/6 animals the rhythms are classically synchronized to the L/D cycle with a maximal activity during the dark period, mainly at its beginning. In the AN mice, without exception, the rhythms are free running. In the bi and mono animals they are either synchronized to the L/D cycle, or synchronized but phase shifted in comparison with C57 Black/6, or free running. For the mono and bi animals, the typical or atypical mode of synchronization of their rhythms to the L/D cycle appears to be correlated with the ganglion cell density. It is well known that such a retinal component ensures the retino-hypothalamic connections. In the C57 Black/6 and AN mice, differential pulse voltammetric measurements of 5-hydroxyindoleacetic acid (5-HIAA, peak 3) extracellular concentrations have been also realized together with polygraphic recordings of the sleep/waking cycle. In both strains, the height of the 5-HIAA peak 3 recorded in the cortex is always the highest during active waking, and decreases during slow wave sleep and paradoxical sleep. Further, a circadian variation of this signal is superimposed to that of the waking state amount. Such circadian variations are synchronized to the L/D cycle in C57 Black/6 animals and free running in the AN mice.

Animals↗

PubMed1990

Voltammetric detection of the release of 5-hydroxyindole compounds throughout the sleep-waking cycle of the rat.

In the present work, differential pulse voltammetry (DPV) measurements of the extracellular fraction of 5-hydroxyindole compounds were performed in rats under long-term chronic conditions. In the nucleus Raphe Dorsalis (n.RD), the voltammetric signal measured at +300 mv (peak 3) disappeared completely 70 to 90 min after injection of Clorgyline (10 mg/kg), a monoamine oxidase inhibitor type A (MAOI-A); the signal measured in such conditions is thus dependent upon extracellular 5-hydroxyindoleacetic acid (5-HIAA peak 3). Deprenyl, an MAOI type B, at the same dose, induced only a slight increase in peak 3 height; according to the fact that MAO-B is selectively located in the 5-HT neurons and since their inhibition does not decrease 5-HIAA peak 3 nor the endogenous 5-HIAA content as measured with High Performance Liquid Chromatography (HPLC), 5-HIAA measured with DPV in the extracellular fluid of untreated animals might come from 5-HT released and metabolized by MAO-A outside the 5-HT neurons. In animals implanted for measurements of both voltammetric and polygraphic parameters, the 5-HIAA peak 3 measured mainly in the anterior and ventral part of the n.RD exhibited large increases in its height during slow-wave sleep (SWS: +39%) and paradoxical sleep (PS = +71%) as compared to the waking state (W = 100%); these variations could reflect the dendritic release of 5-HT. In the Caudate nucleus (n.Cd) the same voltammetric signal presented reverse fluctuations, i.e. an increase during W and a decrease during SWS and PS.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1990

Proopiomelanocortin (POMC)-derived peptides and sleep in the rat. Part 1--Hypnogenic properties of ACTH derivatives.

The sleep-wake effects of the proopiomelanocortin (POMC)-derived peptides, i.c.v. injected, are reported. Adrenocorticotropic hormone (ACTH, 1 microgram) induces an awakening effect, while its two derivatives, desacetyl-alpha-MSH (des-alpha-MSH, 1ng) and corticotropin-like intermediate lobe peptide (CLIP, 10 ng), are respectively able to increase slow wave sleep (SWS) and paradoxical sleep (PS); the hypnogenic effect of CLIP is also observed in hypophysectomized rats. Furthermore, two hypothalamic factors known to be involved in the control of POMC derivatives were also injected; MSH inhibiting Factor (MIF) does not influence the vigilance states, while Corticotropin Releasing Factor (CRF, 1 microgram) increases the waking state. Finally, some preliminary results, obtained with a restraint stress and suggesting a possible interrelation between stress, sleep and POMC derivatives, are discussed.

Adrenocorticotropic Hormone↗

PubMed1990

Proopiomelanocortin (POMC)-derived peptides and sleep in the rat. Part 2--Aminergic regulatory processes.

Apomorphine (Apo), a D1/D2 Dopamine (DA) agonist, at high doses (500 micrograms/kg) induces a short-lasting insomnia, antagonized by a secondary injection of corticotropin-like intermediate lobe peptide (CLIP, 10 ng); these effects are also observed with hypophysectomized (hypoX) rats. The administration of the serotonin (5-HT) agonist 8-hydroxy-2-di-n-propylamino-tetralin (8-OHDPAT, 0.3 mg/kg) induces also an insomnia which, unlike Apo, is followed by a significant PS rebound. CLIP, again, antagonizes the 8-OHDPAT-induced insomnia. Finally, Bromocriptine (5 mg/kg), an agonist for both DA and 5-HT, induces first an insomnia (antagonized by CLIP), followed by a PS rebound; these effects persist in hypoX rats.

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

PubMed1989

[Role of hypothalamic adenosinergic systems in regulating states of wakefulness in the rat].

Immunohistochemical localization of adenosine deaminase (ADA), marker for the putative neurotransmitter/neuromodulator adenosine, has revealed a population of ADA-positive neurons in the ventrolateral hypothalamus in the rat brain. These posterior neurons possess adenosine uptake sites. We have studied the effects of local injections of adenosinergic drugs on the sleep-wake cycle in the rat. Microinjection of erythro-9-(hydroxy-2, nonyl-3) adenine (EHNA), a specific inhibitor of adenosine deaminase, resulted in a significant decrease in wakefulness (W) and an increase in deep slow wave sleep (SWS, or S2) and paradoxical sleep (SP). On the other hand, microinjections of soluflazine, a nucleoside transport inhibitor, increased W and decreased total sleep. These opposite modifications may reflect opposite variations in the extracellular concentrations of Ado and consequently different responses of A1/A2 adenosine receptors.

Adenine↗