Biomedical subjects

J L Valatx

Publications and source records attributed to J L Valatx.

At least 19 recordsLinked to original sources

PubMed1999

Hypoprolactinemic rats under conditions of constant darkness or constant light. Effects on the sleep-wake cycle, cerebral temperature and sulfatoxymelatonin levels.

In genetic hypoprolactinemic rats under light-dark (LD) conditions, the circadian rhythms of slow-wave (SWS) and paradoxical (PS) sleep display an alteration of their phase relationship. The aim of our study was to investigate the effects of constant darkness (DD) or constant light (LL) on the daily distribution and amounts of sleep-wake stages, cerebral temperature and concentrations of the urinary melatonin metabolite, 6-sulfatoxymelatonin, in prolactin-deficient rats. After 3 weeks of DD, the SWS period was 24 h 8+/-6 min and the acrophase occurred at 15:44+/-1:35, while for PS, the period was more stable than during LD (24 h 10+/-8 min vs. 24 h 55+/-43 min) and the acrophase occurred at 16:44+/-1:54. Under LL conditions, circadian sleep rhythms persisted during the first 3 days, then completely disappeared during the third week, to be replaced by ultradian rhythms (period of 4-6 h). Time-series analysis showed that the two sleep states became synchronous as early as the second day under constant conditions. The total amount of PS was increased under both conditions (LL and DD) at the expense of duration of waking. Under LD and constant conditions, the pattern of changes in cerebral temperature was similar to that for wakefulness (W). Sulfatoxymelatonin was rhythmically secreted under both LD and DD conditions, whereas, under LL conditions, its rhythm was abolished. The results show that, in IPL rats in the absence of a zeitgeber, the PS and SWS rhythms recover a synchronous phase relationship and PS amounts are increased.

Animals↗

PubMed1999

The effects of spinal or mesencephalic transections on sleep-related erections and ex-copula penile reflexes in the rat.

The neural mechanisms of penile erections during paradoxical sleep (PS) remain unknown since it has yet to be the subject of neurophysiological investigation. Using a new experimental model for sleep-related erection research in freely behaving rats, neural transections were undertaken to definitively elucidate the effects of paraplegia on PS-related erections and to determine at which brain level the mechanisms underlying PS erectile activity are generated. Continuous polygraphic recordings, as well as ex-copula penile reflexes, were performed in male Sprague Dawley rats before and after spinal (n = 4) or mesencephalic (n = 6) transections. Spinal transections virtually eliminated PS-related erections. Following mesencephalic transections, PS remained qualitatively intact in all rats. PS erectile activity, however, was severely disrupted, as shown by a significant decrease in the total number of erections, the number of erections per hour, and the percentage of PS phases exhibiting an erectile event. Finally, spinal and mesencephalic transections had contrasting effects on ex-copula penile reflexes. Spinal transections significantly shortened the latency to reflex induction and increased the percentage of tests eliciting an erectile event, whereas mesencephalic transections significantly increased the latency to reflex induction without affecting the percentage of tests eliciting an erectile event. These data suggest that the brainstem is not sufficient for the generation of PS erectile activity even though it is sufficient for the generation of other classic PS phenomena. We conclude that neural structures rostral to the mesencephalopn (i.e., the forebrain) are essential for the maintenance and integrity of PS related-erections. The reflex erection data suggest that spinal transection removes a tonic descending inhibition of erections, whereas such an inhibition not only remains intact, but appears enhanced following mesencephalic transection. We hypothesize that the forebrain plays a facilitatory role in erectile control, at least in part, through disinhibition of brainstem tonic anti-erectile mechanisms.

Animals↗

PubMed1999

Quantitative trait loci approach to the genetics of sleep in recombinant inbred mice.

Sleep is a complex trait controlled by many genes, the environment, and probably by gene-environment interactions. Among different approaches to the genetics of sleep, analysis of quantitative traits (QTL) has the advantage of being able to detect, along with major genes, minor and/or modifier genes influencing different quantitative aspects of sleep. We have used QTL analysis in two different sets of recombinant inbred (RI) strains and sought for confirmation of several localizations in eight histocompatibility congenic strains. Several QTLs were identified which influenced the amount of vigilance states. In a first RI series (seven strains) the only QTLs identified were those affecting paradoxical sleep (PS), whereas analysis in a second RI series (25 strains) revealed QTLs influencing PS, slow-wave sleep, and total sleep. Among these, a single QTL on chromosome 5 was associated with all vigilance states, suggesting the presence of a major gene influencing a basic aspect of sleep amount. Search for candidate genes around the identified QTLs indicated several immune related genes that have been implicated in sleep regulation. Transgenic animals carrying loss-of-function and/or gain-of-function mutations affecting these candidate genes should confirm these findings.

Alleles↗

PubMed1999

Human insulin gene insertion in mice. Effects on the sleep-wake cycle?

Recently, insulin synthesis and the presence of an insulin receptor have been demonstrated in the brain. Intracerebroventricular infusion of insulin causes a selective increase in the amount of slow-wave sleep. In the present study, the sleep-wake cycle of transgenic mice, with or without habenular neuronal expression of the human insulin gene, was studied to investigate the possible role of brain insulin as a sleep modulator. Slow-wave sleep duration was increased in those mice expressing human insulin in the habenula. However, it is possible that this effect was not due to expression of the insulin transgene, but to the genetic background of one of the parental strains (CBA) used for insertion of the transgene. Users of transgenic mice should be aware of this possibility and be cautious in interpreting results when hybrid embryos are used as transgene recipients.

Animals↗

PubMed1998

Noradrenaline neurotoxin DSP-4 effects on sleep and brain temperature in the rat.

N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) has a selective degenerative effect on noradrenergic fibers originating from locus coeruleus (LC) neurons. In the present study, we studied its effect on vigilance states and brain temperature by continuous recordings for periods of 1-5 days and 2-4 weeks following DSP-4 treatment. On the first day, paradoxical sleep duration was significantly decreased (-67%, P < 0.05), slow-wave sleep (SWS) duration increased (+16%, P < 0.05) up to 48 h after DSP-4 treatment (+8%, P < 0.05) and the wake period decreased (-8%, P < 0.05). The vigilance states returned to control values 4-5 days later. The brain temperature was decreased during the first night (-2 degrees C) and then recovered the control values. Two and 4 weeks after DSP-4 treatment, paradoxical sleep was still decreased (-18% and -23%, respectively, P < 0.05), while SWS was significantly increased only at night during the fourth week (+23%, P < 0.05). These results therefore provide evidence for a differential involvement of the noradrenergic LC system in sleep mechanisms depending on the light-dark cycle. Different hypotheses are proposed.

Adrenergic Agents↗

PubMed1998

Involvement of stress in the sleep rebound mechanism induced by sleep deprivation in the rat: use of alpha-helical CRH (9-41).

A previous study demonstrated the efficacy of the corticotropin-releasing hormone (CRH) receptor antagonist, alpha-helical CRH (9-41), in blocking the paradoxical sleep increase induced by stress. In the present study, this peptide was used to evaluate the involvement of the stress component of the sleep deprivation, in the paradoxical sleep rebound. Rats were subjected for 10 h to the classical water-tank sleep-deprivation technique and were given, every 2 h throughout the sleep deprivation period, intracerebroventricular injections of either 100 microg/5 microl of alpha-helical CRH (9-41) or vehicle alone. Continuous recordings showed that antagonist treatment decreased the PS rebound, but not the SWS rebound, following sleep deprivation. These findings suggest that, in the water-tank sleep deprivation method, stress, acting via CRH activation, is the main factor inducing the paradoxical sleep rebound.

Animals↗

PubMed1997

Localization of candidate genomic regions influencing paradoxical sleep in mice.

Quantitative trait loci (QTL) approach was used in CXB recombinant inbred mice for preliminary identification of candidate regions on the mouse genome that influence sleep. The only provisional QTLs identified were associated with paradoxical sleep (PS). PS during the light period was associated with markers on chromosome 7 between 7 and 20 centimorgan from the centromere. For PS during the dark period, a single QTL was identified on chromosome 5, near the Clock gene. The 24 h amount of PS was influenced by markers on chromosomes 2, 17, and 19. This first QTL mapping study strongly suggests that a complex behaviour like PS can be controlled by only a few genes.

Animals↗

PubMed1997

Monoamine oxidase B (MAOB)-containing structures in MAOA-deficient transgenic mice.

Monoamine oxidase (MAO)-containing structures were studied for the first time in type A MAO (MAOA)-deficient transgenic mice (Tg8) derived from C3H strain, using MAO enzyme histochemistry. In this mutant line, MAOA activity was not detected in neurons of the locus coeruleus. In contrast, in their dorsal raphe neurons, we noted an intense activity of type B MAO (MAOB). Based on pharmacological MAOA suppression experiments employing a specific inhibitor (clorgyline), we confirmed that the localization of MAOB-positive structures are not different between Tg8 mutant and normal C3H line. Many of MAOB-positive structures which have not been described previously in the rat, cat and primates were described in this study. In the forebrain, MAOB-containing neurons were discriminated in the striatum, septal nuclei, major island of Calleja, diagonal band, medial forebrain bundle, ventral pallidum and amygdaloid nucleus. Stained neurons in the thalamus and hypothalamus were much more extensively distributed in the mouse than the rat. Pontine laterodorsal tegmental neurons showed MAOB activity. The present data suggest that serotonin, a preferential substrate for MAOA, can be oxidized by MAOB in MAOA-deficient Tg8 mice.

Animals↗

PubMed1997

Electron-microscopic study of MAOB-containing structures in the nucleus accumbens shell: using MAOA-deficient transgenic mice.

MAOB-containing structures in the nucleus accumbens were ultrastructurally studied for the first time, using MAOA-deficient transgenic mice and MAO enzyme histochemistry. Among the striatal structures, the nucleus accumbens, and in particular its dorsal shell, showed the strongest MAOB activity. MAOB-active cell bodies were embedded in a dense MAOB-active fiber plexus. MAOB-positive terminals formed axo-dendritic synapses which were exclusively of the asymmetric type. It is suggested that dopamine in the nucleus accumbens shell is transported into MAOB-positive fibers where it is degraded by MAOB.

Animals↗

PubMed1997

Effect of intracerebroventricular administration of alpha-helical CRH (9-41) on the sleep/waking cycle in rats under normal conditions or after subjection to an acute stressful stimulus.

It has been shown in a previous study that specific lesioning of the noradrenergic system of the locus coeruleus abolished the sleep increase induced by immobilization stress. Given the fact that brain corticotropin-releasing hormone (CRH) acts as a neurotransmitter in the locus coeruleus under stress conditions, the present study was designed to investigate the involvement of CRH in the sleep increase seen after immobilization stress and on the spontaneous wake/sleep cycle. One hundred micrograms of the specific CRH receptor antagonist alpha-helical CRH (9-41), or vehicle alone was injected into the right lateral ventricle 30 min either before subjecting the animals to immobilization stress or before the spontaneous sleep-waking recordings onset. A single intracerebroventricular (i.c.v.) injection of alpha-helical CRH (9-41) had no effect on spontaneous paradoxical sleep but abolished the stress-induced increase, while wakefulness and slow-wave sleep were unchanged under both normal and stressful conditions. We therefore report that the involvement of endogenous CRH in the paradoxical sleep mechanism is dependent on the environmental conditions and suggest that, while the paradoxical sleep increase induced by immobilization stress may be mediated by endogenous corticotropin-releasing hormone, other mechanisms, either CRH-independent or situated at a distance from antagonist activity, may be involved in spontaneous paradoxical sleep. These results show, for the first time, that endogenous CRH may be involved in sleep-waking mechanisms only under stressful conditions and, in particular, as a fundamental component of the paradoxical sleep increase.

Animals↗

PubMed1996

[Mechanisms of dream-sleep-wakefulness cycle].

For the occurrence of each state of sleep (slow wave sleep, paradoxical sleep) there are two neuronal networks. The first one called executive is responsible for the sleep phenomenology; the second called permissive is for the triggering of sleep. Wakefulness depends on a very complex system (10 structures) including the permissive networks which inhibit sleep. Sleep onset is thought as a blockade of the waking state by an antiwake network synthesizing hypnogenic factors. Such a regulation allows to suggest that insomnia is a wake trouble depending on a revisited therapy.

Animals↗

PubMed1996

Role of the locus coeruleus in the sleep rebound following two different sleep deprivation methods in the rat.

The aim of the present study was to assess the involvement of the locus coeruleus in the paradoxical sleep rebound following sleep deprivation in the rat. Animals were sleep-deprived for 10 h before, and after, specific N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) lesioning of the noradrenergic-locus coeruleus system. Sleep deprivation was produced using either an instrumental (water tank) or pharmacological (methylamphetamine) method. After lesioning, the rats submitted to the instrumental method showed a significant decrease in the paradoxical and slow-wave sleep rebounds (-54% and -78%, respectively), while animals receiving metamphetamine did not. Our results suggest that the noradrenergic system of the locus coeruleus is a relevant component of the sleep rebound mechanisms. However, the extent of involvement is dependent on the sleep deprivation method used.

Adrenergic Agents↗

PubMed1996

Distribution of prolactin receptors in the rat forebrain. Immunohistochemical study.

The distribution of prolactin receptors (PRL-R) in the rat brain was investigated for the first time with the immunohistochemical technique using monoclonal antibodies raised against PRL-R purified from rat liver. Granular immunostaining was observed in neurons and along their dendritic processes and fibers. PRL-R like immunoreactive neurons were found in a number of brain areas. There was a very dense labelling in the cerebral cortex (pyramidal cell layer), septal nuclei, amygdaloid complex as well as in the hypothalamus (suprachiasmatic, supraoptic, paraventricular and dorsomedial nuclei). A dense staining was seen in the substantia nigra, habenula and in the paraventricular thalamic nucleus. Immunostaining was also found in the choroid plexus and in the subcommissural organ. Comparison between the present distribution and that of PRL-like immunoreactivity indicates that the density of PRL-R generally corresponds to that of the fibers. However, in some regions densely stained by PRL-R antibody, there are very few PRL-immunoreactive fibers. These results are suggestive of different modes of action of PRL in the brain.

Amygdala↗

PubMed1995

Sleep increase after immobilization stress: role of the noradrenergic locus coeruleus system in the rat.

In a preliminary study we showed that the sleep rebound occurring after sleep deprivation is decreased in rats treated with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), a neurotoxic agent specific for the noradrenergic cells of the locus coeruleus (LC). Sleep deprivation methods not only involve sleep loss, but also stress, which per se may induce an increase in sleep duration. Extensive research showed that the locus coeruleus is involved in stress. To evaluate the participation of LC in this mechanism, the effect of DSP-4 treatment was studied on sleep duration following a short intense stress in the absence of sleep loss. The results showed that the augmentation of sleep after 1 h of immobilization stress is lower in DSP-4-treated rats (slow-wave sleep duration, -24%; paradoxical sleep duration, -52%). These findings suggest that the increase in sleep induced by such a stressor is mediated, at least in part, by the noradrenergic LC.

Adrenergic Agents↗

PubMed1995

Corpus spongiosum penis pressure and perineal muscle activity during reflexive erections in the rat.

This experiment represents the first simultaneous analysis of corpus spongiosum of the penis (CSP) pressure and perineal muscle activity during reflex-induced penile erections in the awake rat and provides new data on the coordination of muscular and vascular events in erection physiology. Nine male Sprague-Dawley rats were implanted with pressure transducers under pentobarbital anesthesia (60 mg/kg) for use in a new technique of chronic erection recording involving simultaneous CSP pressure monitoring and electromyography (EMG) of the ischiocavernosus (IC) and bulbospongiosus (BS) muscles. The association of these physiological measurements with visually scored ex copula erectile events was investigated. Reflexive erectile events were systematically associated with an increase in baseline CSP pressure. Glans erections were associated with dramatic suprasystolic CSP pressure peaks concurrent with BS muscle bursts. Indeed, measures of CSP pressure and BS EMG activity were found to vary significantly with the intensity of glans erection. Flips of the penile body, however, involved small CSP pressure increases and IC bursts. These data demonstrate for the first time that both CSP pressures and perineal muscle activity vary significantly with the intensity of penile erection.

Animals↗

PubMed1995

Prolactin and rapid eye movement sleep regulation.

During the past few years data have accumulated suggesting the involvement of prolactin (PRL) in rapid eye movement sleep (REMS) regulation. Pituitary PRL secretion seems to be, at least in part, sleep-dependent. PRL is also found in the central nervous system. PRL-containing neurons in the hypothalamus project to various structures in the brain. Systemic injection of PRL promotes REMS in rats, cats and rabbits. Intracerebroventricular injection of PRL enhances REMS in rats. Stimulation of endogenous PRL secretion by vasoactive intestinal peptide (VIP) also promotes REMS. Immunoneutralization of blood-borne PRL slightly reduces REMS. Various observations (hypoprolactinemic and hyperprolactinemic rats) indicate that PRL may act on REMS via modulating the diurnal rhythms of REMS. It is likely that hypothalamic PRL is more important for sleep regulation than circulating PRL. Hypothalamic PRL is likely involved in the mediation of the REMS-promoting activity of VIP. We conclude that PRL has a role in REMS regulation.

Animals↗

PubMed1994

Experimental evidence of penile erections during paradoxical sleep in the rat.

We have developed a new technique to chronically monitor penile erections in the rat across behavioural states. This technique, involving chronic erectile tissue pressure monitoring and simultaneous ischiocavernosus and bulbospongiosus (IC-BS) muscle electromyography, demonstrates for the first time that rats exhibit penile erections during paradoxical sleep (PS). No erectile events were observed during slow wave sleep. These PS-related erectile events were similar to visually confirmed, waking state, erections in that they were associated with an increase in baseline erectile tissue pressure and, with IC-BS muscle bursts, dramatic suprasystolic penile pressure peaks often greater than 1000 mmHg. PS-related erections were 11 +/- 7 s in duration and were observed in 28.5% of all PS episodes. This method of chronic penile erection monitoring in the rat provides a new animal model for investigating neural mechanisms of sleep-related erections.

Animals↗

PubMed1994

Hypothalamic injection of prolactin or its antibody alters the rat sleep-wake cycle.

Several studies have suggested an interaction between prolactin and the sleep-wake cycle. In this study ovine prolactin (oPRL) and anti-prolactin antibody were microinjected into the rat dorsolateral hypothalamus, which contains prolactin-like immunoreactive neurons. Results indicate that during the light period, prolactin injection induced an increase in paradoxical sleep duration, whereas it caused a decrease when injected during the dark period. Anti-prolactin antibody injection during the dark period also decreased paradoxical sleep duration. There was no effect of oPRL or antibody on slow wave sleep duration irrespective of injection time. These results suggest that prolactin injection may have an inhibitory effect on hypothalamic prolactin neurons.

Animals↗