Biomedical subjects
Publications and source records attributed to M Jouvet.
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In p-chlorophenylalanine (PCPA) pretreated insomniac cats, the intraventricular (i.v.t.) injection of artificial cerebrospinal fluid (CSF) did not impair the insomnia. CSF transfer from normal cats was followed in 4 out of 9 cats by the restoration of paradoxical sleep (PS). However, CSF transfer from paradoxical sleep deprived cats did result in 12 out of 13 experiments in a significant increase in slow wave sleep (SWS) and the induction of PS. Biochemical analysis of the CSF from normal or PS deprived cat has shown that the highest quantity of indolamines was at least 1000 times smaller than the threshold dose of 5-HTP (200 microgram) which has been shown to be able to restore sleep by i.v.t. injection in PCPA pretreated insomniac cats. These experiments provide evidence that the transfer of a small quantity of CSF (250 microliter) from a previously paradoxical sleep deprived cat can restore paradoxical sleep in an insomniac PCPA pretreated cat in bypassing the biosynthesis of serotonin (5-HT). These results suggest that a 'paradoxical sleep inducing factor' may be stored in the central nervous system during sleep deprivation.
A fluorescence histochemical study of the pontine catecholaminergic (CA) neurons of two inbred strains of mice, BALB/c (C) and C57BL/6 (B6) and their F1 hybrids revealed that the total number of the fluorescent cells in the C strain was 38% lower than that of the B6 strain. In F1 hybrids, the total number of neurons was not statistically different from that of the B6 parent. During the development from birth to adulthood, the same quantitative differences between strains were observed.
Behavioral, polygraphic, biochemical and histological aspects of thiamine deficiency in rats induced by thiamine-deficient food and pyrithiamine treatment (40 mg/kg daily for 4 days) are described. Behavioral alterations were essentially characterized by ataxia, pilo-erection and paresis. Polygraphic data indicated an increase in slow-wave sleep (SWS) of 33% and decreases in paradoxical sleep (PS) and wakefulness (W), respectively, of 69% and 27%. These effects were reversed by complete food and thiamine administration, the reversal including an overshoot in PS. Biochemical assays, performed when the polygraphic data indicated a large effect, demonstrated a significant increase in serotonin (5-HT) and 5-hydroxyindolacetic-acid (5-HIAA). These effects were particularly evident in the raphe system and the locus coeruleus. Histological data from the raphe dorsalis displayed a notable increase in yellow fluorescence in pyrithiamine-treated animals over controls. We conclude from these experiments that a deficiency in thiamine affects the serotonergic system and that the subsequent effects on sleep are a consequence of this serotonergic change.
Local cerebral glucose utilization (LCGU) was measured during spontaneous waking and slow wave sleep (SWS) by an adaptation of the [14C]deoxyglucose method to the free moving cat. In awake animals heterogeneous rates of LCGU were observed throughout the brain with values extending from 8 mumol x 100 g-1 x min-1 for white matter, to 113 for the inferior colliculus. There was no significant difference for LCGU in SWS compared with awake animals.
When injected intraperitoneally (i.p.) into normal cats, methiothepin (1-7.5 mg/kg) or metergoline (0.5-8 mg/kg) induced total insomnia. The duration of suppression of deep slow-wave sleep (SWS2) and paradoxical sleep (PS) was dose-related for methiothepin (10-30 h), but was shorter and not dose-related for metergoline (3-5 h). When injected into the fourth ventricle, methiothepin (20 microgram) induced a selective suppression of PS for 6-7 h). In rho-chlorophenyl-alanine (PCPA)-pretreated, insomniac cats, i.p. injection of 5 mg/kg of DL-5-hydroxytryptophan(5-HTP) was followed by SWS and PS after latencies of 25 and 62 min. When methiothepin (2.5 mg/kg) or metergoline (4 mg/kg) were given before 5-HTP, the latency for the first PS episode increased dramatically to 7 h. Thereafter PS occurred periodically for 10 h but no SWS appeared. These results suggest that a 'PS factor' induced by 5-HTP and different from indolamines is preserved during the antagonistic effect of methiothepin or metergoline until it can act upon the executive mechanisms of PS. Our data also suggest that metergoline and methiothepin suppress but do not delay the mechanism responsible for SWS2 in the PCPA-5-HTP paradigm.
The distribution of enkephalin (Enk) and tyrosine hydroxylase (TH) immunoreactivity in the cat locus coeruleus (LC) has been studied with indirect immunofluorescence technique. After intratissular injection of colchicine numerous enkephalin-containing cell bodies were seen throughout the rostrocaudal extent of the LC complex. Comparison of 8 micrometers-thick consecutive sections treated with antiserum to Enk of TH, a specific marker for catecholaminergic neurons, shows that most cells containing TH also present Enk immunoreactivity. This study provides the first evidence for the coexistence of enkephalin and catecholamine in CNS neurons.
Glucose utilization (GU) was measured during spontaneous waking and slow-wave sleep (SWS) by adaptation of the [14C]deoxyglucose method to the unrestrained cat. In sleeping animals a greater autoradiographic signal between choroid plexus (CP) and the rest of brain was noticed. Quantification provided an index of the metabolic rate of CP and confirmed that mean values for GU were significantly higher in "sleeping' than in "awake' cats.
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Bilateral or unilateral, localized and reversible cooling (+10 degrees C) of the anterior part of the locus coeruleus area (LCp) in the cat induced, in rapid succession, slow wave sleep (SWS) and a transitory phase of SWS + PGO. These states of sleep were followed in 40-50% of the animals by paradoxical sleep (PS). These effects (on SWS, SWS + PGO and PS) occurred following repetitive periods of short duration cooling and were maintained during long duration cooling (70 min). Unilateral cooling of the ventral part of the locus coeruleus area (LC alpha) and peri-LC alpha induced wakefulness, regardless of the states of sleep in which the cooling was performed. After a cryolesion (-24 degrees C) of the nucleus raphe dorsalis, cooling of the LCp did not induce a hypnogenic effect. Electrical stimulation of the locus coeruleus area, however, always induced wakefulness.
We have compared the effects of electrolytic and kainic acid lesions of the pontine gigantocellular tegmental field (FTG) upon paradoxical sleep (PS). Following bilateral electrolytic destruction of the ventrolateral part of the FTG, there was an almost total suppression of PS which lasted at least for 5 weeks. Muscular atonia was absent and ponto-geniculo-occipital (PGO) activity was reduced by 80% in the few remaining episodes of PS. Contrary to to these effects, total neuronal cell loss of the FTG induced by bilateral kainic acid injection was not followed by a significant quantitative and qualitative alteration of PS. These results indicate that the neurons located within the FTG are not critical for the generation of both phasic and tonic components of PS. Elimination of this state of sleep after electrolytic destruction of the ventrolateral pontine reticular formation can be explained by interruption of fibers connecting the region of the locus coeruleus complex and the bulbar reticular formation.
The intraventricular injection of 100 ng of vasoactive intestinal polypeptide (VIP) is followed by a significant increase of paradoxical sleep in the Rat. In P. chlorophenylalanine pretreated insomniac Rats which do not present spontaneous paradoxical sleep episodes, intraventricular injection of VIP induces normal quantities of this state of sleep.
In vitro, differential pulse voltammetry combined with electrochemically treated carbon fiber electrodes enabled detection, in different solution of 5-hydroxyindole compounds, of an oxidation peak 3 at +300 mV. In vivo, a striatal peak 3 was also recorded at this potential. Electrolytic or 5,7-dihydroxytryptamine lesions interrupting the medial forebrain bundle (MFB) were followed by a decrease of 65% and 64% in peak height, but not elimination of the peak. Biochemical determinations were significantly correlated to the peak 3 measurements. The existence of peak 3 as well as hydroxyindole compounds in blood suggested a blood contamination under the experimental conditions employed. This possibility is confirmed both by the complete disappearance of striatal peak 3 in animals with the MFB lesioned and surgically prepared a week before recordings, and by biochemical measurements in parachlorophenylalanine-treated or perfused (phosphate-buffered saline solution) animals.
Differential pulse voltammetry with electrochemically treated carbon fiber electrodes was used to study, in anesthetized rats, the alterations of the striatal electrochemical signal appearing at +300 mV (peak 3), following pharmacological manipulation of the animals. Decreases in peak 3 were obtained after injections of NSD 1015, Ro 4-4602 and Clorgyline. This, in conjunction with biochemical measurements, suggested that 5-hydroxyindoleacetic acid (5-HIAA) is, to a considerable extent, responsible for this electrochemical signal. Increases in peak 3 obtained after reserpine, L-tryptophan and D,L-5-HTP, as well as biochemical data reinforced this hypothesis, as did the detection of peak 3 in cerebrospinal fluid and its increase after probenecid injection. The occurrence of a feed-back mechanism is discussed following injection of D,L-5-HTP.
Differential pulse voltammetry used in combination with an electrochemically treated carbon fiber electrode allowed to detect ascorbic acid (AA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum of unanaesthetized freely moving rats. Carbon fiber electrodes were implanted under light halothane anaesthesia. When the rat recovered from anaesthesia, voltammograms were recorded every 2.5 min for about 5 h. During the last 3 h the signals corresponding to AA and DOPAC appeared stable and reproducible, allowing comparisons between control and pharmacological experiments. After the in vivo experiments, the electrodes were calibrated in AA and DOPAC solutions. Striatal AA and DOPAC levels were thus estimated to be 306 and 17.7 microM respectively. DOPAC signals were increased by haloperidol and chloral hydrate, decreased by amphetamine and suppressed by pargyline. In pargyline pretreated rats the catechol signal slightly re-appeared after amphetamine injections. This signal was attributed to dopamine (DA) and estimated to a concentration less than 50 nM DA. The AA current recorded in the striatum was not modified when dopaminergic terminals selectively degenerated. The AA signal was decreased by chloral hydrate or halothane anaesthesia and increased by amphetamine injections. This latter effect depended on the presence of dopaminergic terminals. This shows that the increasing current effect of amphetamine, previously observed by non-selective techniques, should be attributed to AA rather than DA. These results confirm that the catechol compound electrochemically detected in the striatum is the direct metabolite of the DA, i.e. DOPAC, and support the thesis of a functional relationship between AA levels and dopaminergic neurotransmission.
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Differential pulse voltammetry (DPV) was used in conjunction with electrochemically treated carbon fibre microelectrodes to monitor in vivo the catechols (CA) levels in the substantia nigra (SN), ventral mesencephalic tegmentum (VMT) and nucleus accumbens of anaesthetized rats. The current corresponding to CA oxidation was always closely related to the anatomical localisation of the dopaminergic neurons e.g. it was maximal in tht pars compacta of the SN. In addition, the current was selectively suppressed in all regions after 6-OHDA-induced degeneration of the dopaminergic neurons and after pargyline treatment. These findings together with our previous results suggest that 3,4-dihydroxyphenylacetic acid (DOPAC) is the main contributor to the CA oxidation current measured in these areas. Haloperidol induced a significant increase of the CA signal in the nucleus accumbens (+70%) but not in the SN or VMT. The DOPAC concentrations declined exponentially after pargyline administration. The fractional rate constant of DOPAC, computed from these results appears to be similar in all regions studied except for n. accumbens where the low rate of disappearance might be responsible for the high DOPAC concentration measured in this area. In conclusion, DPV with electrochemically treated carbon fibre electrodes is a useful means of monitoring extracellular DOPAC levels in dopaminergic brain regions.
Local cerebral glucose utilisation (LCGU) was measured with the [14C] deoxyglucose ([14C] DG) method in the awake, free moving Mouse. Values vary from 112 mumoles. 100 g-1. min.-1 in the superior colliculus, the most active structure, to 22 mumoles. 100 g-1. min.-1 in the internal capsule. Glucose consumption is high in fasciculus retroflexus, a result peculiar to the Mouse when compared to the other Mammals were studied so far with this method. The modifications in plasma sampling proposed in this paper should facilitate the use of the [14C] DG method in free moving animals as small as the Mouse, and allow for study of the effects of behavior on local cerebral energy consumption.