Biomedical subjects
Publications and source records attributed to M Jouvet.
We have shown the presence of a specific binding of 5 hydroxytryptophan in the red nucleus and oculomotor nucleus of the Rat brain. The analysis of the saturation curve carried out on a membrane preparation suggests the existence of a high affinity binding site (Kd = 1 nM).
Using immunohistochemical techniques, we demonstrated oxytocin (OT) and vasopressin (AVP) neurons in the cat hypothalamus. The OT immunoreactive neurons were found mainly in the paraventricular nucleus, supraoptic nucleus and dorsal accessory group located lateral to the fornix. In addition to these hypothalamic structures, the AVP immunoreactive neurons were observed in the suprachiasmatic nucleus, ventral accessory group located in the retrochiasmatic area and lateral accessory group, dorsal to the supraoptic nucleus caudally, and ventral to the medial part of the internal capsule rostrally. We further demonstrated a different localization of the OT and AVP immunoreactive neurons in the paraventricular and supraoptic nuclei.
In chronic pontine cats without hypothalamo-hypophysis, daily subcutaneous or intraventricular injection of total extracts of Bovine neuro-intermediate lobe increases both survival and quantity of paradoxical sleep, while synthetic Lysine vasopressin, Oxytocin or ACTH have no effect. Chronic pontine cats with "isolated hypophysis" have a longer survival and a more significant amount of paradoxical sleep than those without hypothalamo-hypophysis. Factor(s) liberated by pars intermedia are very likely to be responsible for the increase of PS since only pars intermedia remains functional in the "isolated hypophysis" as shown by immunocytochemical controls.
The in vivo voltammetric signal of 5-OH-indoles increased or decreased in the ventricular cerebrospinal fluid when body temperature was artificially increased or decreased in rats in acute experiments. The increase of the signal occurring after raising the body temperature was facilitated by premedication with the monoamine oxidase inhibitor pargyline. It was not abolished by pretreatment with the serotonin synthesis inhibitor para-chlorophenylalanine, although the latter caused an 85% decrease of ventricular 5-OH-indole level. No similar effects were demonstrable in the 5-OH-indole signal of the caudate nucleus recorded simultaneously. An increase of the 5-OH-indole peak was found also in animals chronically implanted with voltammetric electrodes when the ambient temperature was increased in their cages. According to the results of in vitro experiments, a direct physical effect of changes in brain temperature on the sensitivity of the voltammetric electrodes cannot account for changes found in the cerebrospinal fluid. These data, therefore, demonstrate that the increase of body temperature is followed by an increase of 5-OH-indole concentration in the ventricular cerebrospinal fluid. The in vivo voltammetric technique appears to be a suitable method for studying the serotonergic mechanisms involved in thermoregulatory processes.
This study concerns the voltammetric signal appearing at a +300 mV potential (peak 3) recorded from the suprachiasmatic nuclei (SCN) of rats under acute and chronic conditions. In acute conditions, and in order to accurately localize the working electrode, a topographical study of the peak 3 height was first realized in the frontal plane containing the SCN by use of differential pulse voltammetry and monocarbon fiber electrodes. In the same conditions, the effects of clorgyline and reserpine were studied. Clorgyline decreased peak 3 while reserpine increased it. Contrary to 5-HT, 5-HIAA contents of the SCN, measured with high performance liquid chromatography, demonstrate analogous variations. All these data suggest that it is essentially 5-HIAA which is responsible for peak 3 from the SCN. In unanesthetized, freely moving rats, under a 12/12 h light-dark cycle, spontaneous and circadian variations of the SCN's peak 3 were studied, during the rest-activity cycle. Multifiber working electrodes were used for this purpose. During spontaneous and successive periods of rest and activity peak 3 height was always found to be higher during activity. Further, these spontaneous variations were superimposed with a circadian variation exhibiting its acrophasis during the dark period. Our data suggest that the release and catabolism of serotonin is greater in waking than in sleeping animals. They also suggest, that the rostral raphe system, phase locked with the SCN, plays an important role in the circadian variations measured.
The effect on the sleep-waking cycle of low intensity electrical stimulation (0.2 mA intensity, 80 Hz frequency, 0.7 ms signal duration) within the lateral ventricles was studied in rats maintained under a photoperiod of 12 h light and 12 h darkness (lights on at 06.00 h). When stimulation was performed at 1700 h for 3 min, there was a significant immediate increase in paradoxical sleep (PS) and slow wave sleep (SWS) during the hours of darkness, followed by a delayed increase in diurnal PS amounts during subsequent days. These results are discussed with reference to mechanisms involving the pineal gland and serotonergic system on both the immediate and long-lasting PS effects.
Nuclei raphe dorsalis (RDN) and magnus (RMN) were simultaneously studied using the differential pulse voltammetry (DPV) technique in chronic freely moving rats during their sleep-waking cycle. Parallel variations in peak 3 (due to 5-hydroxyindoles) were observed in both these areas: the peak 3 heights were maximum in both RDN and RMN during waking (W), decreased in slow wave sleep (SWS) and were minimum in paradoxical sleep (PS). Monoamine oxidase inhibitor (MAOI) treatments induce at first a decrease of peak 3 (-50% compared to the control values), but there was a subsequent increase (+100% compared to the control values). This suggests that 5-hydroxytryptamine (5-HT) can contribute to peak 3 measured in vivo.
Differential pulse voltammetry using a new type of carbon fiber electrode, electrochemically treated, is described. The working electrode contains 3 pyrolytic carbon fibers, and passes more current, thus giving a greater sensitivity (with the PRG5 Tacussel polarographic system) than the original monofiber electrodes. It is now possible to investigate brain areas where the monofiber electrodes, working near the limit of PRG5 sensitivity, showed too small a signal. These electrodes have, in addition, better mechanical resistance and can be used (after trypsin cleaning and further electrochemical treatment) for several experiments. Electrochemical measurements made in the nucleus raphe dorsalis before and after treatment with p-chlorophenylalanine, reserpine, clorgyline and clorgyline followed by reserpine, suggest that as in the striatum 5-hydroxyindoleacetic acid (5-HIAA) is mainly responsible for peak 3. The map of the raphe system made with this technique is well correlated with the serotoninergic system of the raphe: the highest peak heights are recorded in the raphe dorsalis.
The administration of p-chlorophenylalanine (PCPA), an inhibitor of serotonin (5-HT) biosynthesis, at the end of a 48 h sleep deprivation does not impair the subsequent rebound of deep slow wave sleep (SWS2) and paradoxical sleep (PS). On the contrary, the administration of PCPA during a 48 h sleep deprivation is followed by a great decrease of light slow wave sleep (SWS1) and by total disappearance of SWS2 while some rebound of PS still occurs in narcoleptic-like attacks. These experiments provide evidence that sleep inducing materials are accumulated during sleep deprivation. Serotoninergic processes appear to be involved in the regulatory mechanisms of the biosynthesis and the accumulation of SWS2 and PS factors.
Recordings were made from 24 "PS-OFF" neurons, characterized by a slow rhythmic discharge rate during waking the slow wave sleep and a marked decrease in the firing rate during paradoxical sleep, in the ventromedial medulla oblongata of freely moving cats. These neurons were located in either the nuclei raphe magnus and pallidus or the neighboring reticular formation where serotonin-containing neurons are found in the cat. Two types of medullary PS-OFF neurons are described, and the descending projection and slow conduction velocity of some of these neurons are demonstrated.
S-adenosyl-L-homocysteine (SAH) was administered to normal and pinealectomized rats previously implanted with electrodes for polygraphic recording. In normal rats, injected at 17.00 h, 7 mg/kg SAH induced a significant increase of paradoxical sleep (PS) during the night. When injected at 09.00 or 19.00 h, no effect was observed. In pinealectomized rats, SAH had no significant effect on PS amounts but seemed to resynchronize the PS rhythm. Thus, the pineal gland plays an important role in SAH effect. The results are discussed with reference to different mechanisms within the rat pineal gland and a possible implication of beta-adrenergic receptors.
Long-term sleep recordings of mice from 3 inbred strains showed that the amount of time spent in sleep over successive 24-h periods varied as the subjects adapted to experimental conditions. A sinusoidal type variation, with a period of about 15 days, modulating the basic trends in sleep times is described; but the principal finding of this study relates to a monotonic decrease in Paradoxical Sleep (PS) as recording continued. Age, stimulus deprivation and fatigue effects do not appear to be causative factors for this decrement, indicating that the changes in PS might reflect a habituation process. On this basis it is hypothesized that an increase in PS time in the mouse is a specific response to a significant environmental stimulus and could, therefore, form part of the coping strategy. This hypothesis is generalized and discussed in terms of its implications, both for experimentation concerned with measuring PS times and with the possible functional significance of PS.
The distribution of tyrosine hydroxylase-, substance P- and enkephalin-immunoreactive neurons in the cat dorsolateral pons was studied using the indirect immunofluorescence method of Coons. To allow for the visualization of substance P- and enkephalin-immunoreactive cell bodies, colchicine was injected either in the ventricular space or in the cerebral tissue. The distribution of the tyrosine hydroxylase-immunoreactive cell bodies corresponded with the well-known distribution of catecholamine cells in this area of the brain. The observation of adjacent sections treated separately with tyrosine hydroxylase- and enkephalin-antiserum revealed that most catecholaminergic cells contain enkephalin-immunoreactivity. In addition to this catecholamine-enkephalin cell population, a moderate number of substance P-immunoreactive cell bodies was found in dorsolateral pons. The peribrachial nuclei were found to be densely supplied with substance P- and enkephalin-immunoreactive fibers, whereas the medial subdivisions, which contain the majority of the catecholamine cells in the dorsolateral pons, display a moderate number of immunoreactive fibers. These results are suggestive of interactions between peptide-containing and catecholaminergic neurons and also between-peptide-containing and non-catecholamine-containing neurons in the cat dorsolateral pons.
In rats, chronically implanted for measurements of both voltammetric and polygraphic parameters, variations of the electrochemical signal corresponding to extracellular 5-hydroxyindole compounds (peak 3) were measured during the sleep-waking cycle. The higher amplitude of this signal is always measured during waking. It decreases during slow-wave sleep (20 to 30%) and reaches its lower value during paradoxical sleep (30 to 40%). This phenomenon has been found in all structures investigated, cerebral cortex, caudate nuclei, dorsal hippocampus, suprachiasmatic nuclei, cerebellum, nuclei raphe dorsalis, centralis, pontis and magnus.
Intratissue injection of 1 to 20 micrograms of L-5 HTP in numerous areas of the cat brainstem failed to reverse P-chlorophenylalanine induced insomnia. On the other hand, injection of 2 to 7 micrograms of L-5 HTP in the ventrolateral hypothalamus induced both slow wave sleep and paradoxical sleep after 36 and 76 min.
In the Cat, subcutaneous injections of 2,000 u/kg of Bacitracin, a peptidase inhibitor, induce an important and significant increase of paradoxical sleep. This increase begins after about 3 hrs. following the injection, and lasts for 18th hour.
Through combined retrograde labeling with HRP and serotonin immunohistochemistry, we have demonstrated that ventral and caudal hypothalamic neurons, both non-immunoreactive and immunoreactive to serotonin after administration of 5-hydroxytryptophane, give rise to direct ascending projections to the entire cerebral cortex as well as direct descending projections to the nucleus locus coeruleus alpha in the pontine tegmentum. A retrograde double labeling method with fluorescent dyes further suggested that the population of ascending hypothalamic neurons is different from that of descending ones.
Whereas there are considerable interindividual variations in the temporal patterns of rapid eye movement during paradoxical sleep in young adult Males, these patterns are similar in monozygotous twins.