[Treatment of hypersomnia with modafinil].
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Disorders of Excessive Somnolence↗
Biomedical subjects
M Jouvet
Publications and source records attributed to M Jouvet.
Neonatal monosodium glutamate dosing alters the sleep-wake cycle of the mature rat.
Alterations of the sleep-wake cycle have been studied in male adult rats after neonatal administration of monosodium glutamate (MSG; 4 X 4 mg/g body wt.). Results indicated that MSG treatment caused: an almost complete disappearance of ACTH and alpha-MSH immunoreactive (IR) perikarya in the rostral part of the arcuate nucleus; an increase in total sleep duration with a more pronounced effect on paradoxical sleep. Regarding circadian rhythmicity there was a trend to a decomposition of the 24 h period into ultradian components (12 h, 8 h, 6 h harmonics). The participation of pro-opiomelanocortin peptides in sleep regulation is discussed.
Activity Cycles↗
Possible involvement of the S-adenosyl-L-homocysteine metabolites, adenosine and L-homocysteine, in sleep in rats.
The effects of i.p. injections of adenosine (Ado) and homocysteine at 17.00 h were tested on the rat sleep-waking cycle. Administration of 7 and 50 mg/kg of Ado resulted in a significant increase in sleep in otherwise saline male rats during the environmental-dark period (18.00-06.00 h). Increments of paradoxical sleep were maximal with the smaller dose of Ado. The larger dose increased slow-wave sleep during the first 2 h. In contrast, administration of homocysteine (7 mg/kg) had no effect while a larger dose (50 mg/kg) induced a slight but significant long-lasting decrease of paradoxical sleep. These results were compared with those previously obtained with S-adenosyl-L-homocysteine (SAH), an intracellular precursor of Ado and L-homocysteine. It is proposed that the reported hypnotic action of exogenous SAH in rats could be mediated by Ado receptors.
Adenosine↗
Periventricular dopaminergic neurons terminating in the neuro-intermediate lobe of the cat hypophysis.
The aim of the present study was to determine the exact origins of the dopaminergic hypothalamohypophyseal projections in the cat brain. For this purpose, we used a retrograde tracer technique with horseradish peroxidase (HRP) in conjunction with tyrosine hydroxylase (TH) immunohistochemistry as a marker for the dopaminergic neurons. After injections of the tracer into the neuro-intermediate lobe, a substantial number of HRP-labeled neurons was observed in the supraoptic and paraventricular neurosecretory nuclei. Furthermore, a cluster of HRP-positive neurons was found in the tuberal component of the periventricular nucleus where few, if any, neurosecretory magnocellular cells are identified. TH immunohistochemistry on the same sections further revealed that virtually all these HRP-containing neurons showed TH immunoreactivity. These double-labeled neurons were medium in size and fusiform or ovoid and appeared to belong to the A14 dopamine cell group. In addition to these medium-sized double-labeled neurons, a magnocellular type of double-labeled cell body was identified just adjacent to the organum vasculosum of the lamina terminalis and in and around the supraoptic and paraventricular nuclei. These double-labeled cells appeared to be members of the A14 and A15 dopamine cell groups. In conclusion, the present study indicated that the dopaminergic projections to the cat neurointermediate lobe might originate mainly in the medium-sized cells located in the tuberal periventricular nucleus and partly in the large-sized cells located in and around the supraoptic and paraventricular neurosecretory nuclei.
Animals↗
Distribution of enkephalin-immunoreactive cell bodies in relation to serotonin-containing neurons in the raphe nuclei of the cat: immunohistochemical evidence for the coexistence of enkephalins and serotonin in certain cells.
In this study we have examined the distribution of enkephalin-like immunoreactive (ELI) cell bodies in the cat raphe nuclei pallidus (NRP), obscurus (NRO), magnus (NRM), pontis and dorsalis (NRD) after intraventricular administration of colchicine. All the raphe nuclei examined were observed to contain ELI cell bodies along their whole caudorostral extent. By comparing consecutive sections treated separately with anti-5-HT and enkephalin-antiserum it was observed that certain 5-HT cells in each raphe nucleus contain ELI material. A quantitative estimation was attempted. In NRP and NRO approximately half of the total immunoreactive neuronal population appeared to be immunoreactive for both 5-HT and the enkephalins. In NRM the proportion would be one-third, whereas it seemed almost negligible in NRD. Among the 5-HT cells, approximately two-thirds might be ELI in NRP and NRO, and one-half in NRM.
Animals↗
Distribution of PNMT-immunoreactive neurons in the cat medulla oblongata.
The distribution and morphology of presumptive adrenaline neurons in the cat medulla oblongata were studied in conjunction with the indirect immunoperoxidase technique utilizing antibody raised against bovine adrenal phenylethanolamine-N-methyltransferase (PNMT), an enzyme which converts noradrenaline to adrenaline. Small PNMT-immunoreactive (IR) perikarya are located in the dorsomedial part of the medulla (C2 group) extending from P17 to P12, and larger ones in the ventrolateral part (C1 group) from P11 to P9 of the caudorostral extent. In the rostral medulla (P11-10), larger cells extended more dorsally in the lateral tegmental field, where only a few catecholamine cells are localized. No midline PNMT-IR cells were identified corresponding to C3 cell group in the rat. Distinct longitudinal PNMT-IR axon bundles can be traced through the dorsal part of the lateral tegmental field. Comments are made on the relative localizations of the PNMT-IR and DBH-IR cells, as well as on species differences in comparison with the results reported in the rat.
Adrenal Glands↗
Nocturnal continuous infusion of growth hormone (GH)-releasing hormone results in a dose-dependent accentuation of episodic GH secretion in normal men.
Fluctuations in plasma GH levels have been found in patients with acromegaly who have continuously elevated levels of ectopically produced GH-releasing hormone (GHRH). Likewise, plasma GH fluctuations have been found in normal subjects receiving continuous GHRH infusions. We report the effects of two doses of GHRH, administered by constant infusion, on nocturnal GH secretion in six normal young men. Each received, in random order, 2.5 ng/kg X min GHRH, 15 ng/kg X min GHRH, and 0.15 M NaCl. During both GHRH doses, a highly significant increase in total nocturnal GH secretion was found (P less than 0.001) as well as an increase in GH secretion during different periods of the night. Nocturnal GH secretion was episodic during the GHRH infusions, with an increase in the number and magnitude of the peaks compared to those during the NaCl infusion. Plasma immunoreactive GHRH concentrations plateaued at 1 h during the high dose and at 3 h during the low dose GHRH infusion. Sleep parameters, including total sleep time, sleep latency, and duration and timing of the different sleep stages, were not affected by GHRH infusions. We conclude that GHRH, continuously infused, increases nocturnal GH secretion according to the dose, while the episodic pattern of GH secretion is maintained.
Adult↗
[Epistemology of hypnology].
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Activity Cycles↗
[Role of hypothalamic histaminergic systems in the regulation of vigilance states in cats].
We have studied the effects of local injections of histaminergic and antihistaminic drugs on the sleep-waking cycle in the cat. Microinjections of alpha-fluoromethylhistidine (alpha-FMH), a specific inhibitor of histidine decarboxylase, in the ventrolateral posterior hypothalamus, where histamine-immunoreactive neurons have been recently identified, resulted in a significant decrease in wakefulness (W) and increase in deep slow wave sleep (SWS). On the other hand, microinjections of SKF-91488 (Homodimaprit), a specific inhibitor of histamine-N-methyltransferase, increased W and decreased SWS and paradoxical sleep (PS). Microinjections of histamine also produced an increase of W, while this effect was abolished by pretreatment with mepyramine, an H1-histamine receptor antagonist.
Animals↗
[Increase of paradoxical sleep, induced by injection of ibotenic acid in the ventrolateral posterior hypothalamus in the cat].
The intratissular injection of ibotenic acid into the ventrolateral part of the posterior hypothalamus induced a dramatic biphasic and transient hypersomnia immediately after disappearance of the anaesthesia (14 to 24 hrs. after injection). The duration of hypersomnia was related to the dose of neurotoxin injected. Its first period was characterized by an increase in paradoxical sleep (PS) (300%). Then, during the second phase, PS disappeared and there was a subsequent increase of slow wave sleep (SWS) (60%). Finally, on the third day, all cats recovered control level of PS and SWS.
Animals↗
[Localization of cholinergic neurons in the cat lower brain stem].
The localization of cholinergic neurons in the cat lower brain stem was determined immunocytochemically with a monoclonal antibody against choline acetyltransferase (ChAT), the acetylcholine synthesizing enzyme. ChAT-positive neurons were observed in four major cell groups: cranial nerve motor and special visceromotor neurons: parasympathetic preganglionic visceromotor neurons; neurons located in the ponto-mesencephalic tegmentum including area X (or pedunculopontine tegmental nucleus), nucleus laterodorsalis tegmenti (Ldt) of Castaldi, and peri-locus coeruleus alpha (peri-alpha); and neurons located in nucleus reticularis magnocellularis (Mc) and adjacent nucleus reticularis gigantocellularis (Gc) of the medulla.
Animals↗
[Long-duration insomnia after lesions of the perikaryons of the paramedian preoptic area in cats].
The destruction of paramedian preoptic neurons by intra-tissue injection of ibotenic acid induces, in the cat, the disappearance of deep slow wave sleep and paradoxical sleep for 2 to 4 weeks, while light slow wave sleep is slightly disturbed. This insomnia, well tolerated, is not secondarily associated with central temperature disturbance.
Animals↗
[Histamine-immunoreactive neurons in the hypothalamus of cats].
The localization of histaminergic neurons in the cat brain was determined immunohistochemically with an antibody against histamine. We found that histamine-immunoreactive neurons are observed exclusively in the posterior hypothalamus of colchicine treated cats. The larger group of neurons was found in the ventrolateral part of the posterior hypothalamus, including the tuberomammillary nucleus. Histamine-positive neurons were also observed in the supramammillary area and adjacent posterior hypothalamic area, as well as in the peri- and premammillary regions. In addition, numerous histamine immunoreactive fibers were detected, not only in the posterior hypothalamus, but also in other brain areas, such as the preoptic area of the anterior hypothalamus.
Animals↗
Effects of hypothalamic paraventricular lesions on sleep in rats.
In 7 rats 45-86% of the hypothalamic paraventricular tissue was destroyed by electrolytic coagulations. During the first 6 post-operative days the mean daily amount of paradoxical sleep was significantly decreased, and the circadian sleep-walking cycles of paradoxical and slow-wave sleep were abolished. The slow-wave sleep rhythm then became normal, but in paradoxical sleep the acrophase was shifted, and in one animal the rhythm was completely inversed. Thus the hypothalamic paraventricular nucleus seems to play a modulating role in the production of paradoxical sleep and in the generation of its rhythm.
Animals↗
Differential effects of chronic dehydration on protein synthesis in neurons of the rat hypothalamus.
The rate of methionine incorporation was measured in individual hypothalamic nuclei by a quantitative autoradiographic technique: the L-[35S]methionine method. Physiological stimulation of the hypothalamo-neurohypophysial system by two days of water deprivation, a stress that increased the plasma total neurophysins concentration 4-5-fold, resulted in a 70-80% increase in overall protein synthesis in the supraoptic nucleus and in the magnocellular subdivisions of the paraventricular nucleus. The same stimulus had no effect on protein synthesis rate of the suprachiasmatic nucleus and of the other representative cerebral structures examined. This differential effect on protein synthesis was also observed within the paraventricular nucleus.
Animals↗
Local cerebral glucose utilization in the free moving mouse: a comparison during two stages of the activity-rest cycle.
The 2-deoxy-D[1-14C]glucose ([14C]DG) technique has been applied to the free moving mouse for the quantitative determination of local cerebral glucose utilization (LCGU). Reproducible values for LCGU were obtained indicating that the [14C]DG method had a sufficient resolution power to allow visualization and quantification of very small structures provided that glucose and [14C]DG plasma concentrations were measured on microsamples, autoradiographs prepared from proper tissue sections and suitable techniques used for analysis of the maps thus obtained. LCGU was measured in free moving mice during two stages of the light-dark cycle, one corresponding to a period of rest and the other to a period of high motor activity. In the two groups of animals LCGU was heterogeneous in the grey matter, the highest values being found in the auditory regions, the cerebellar and vestibular nuclei. LCGU was found to be lower in drowsy animals during the day than in active animals during the night and the difference was significant in the 8 following structures: the sensorimotor cortex, the septal nuclei, the nucleus of the olfactory tract, the basal amygdaloid nucleus, the ventral nucleus of the thalamus, the lateral geniculate body, the medial geniculate body and the auditory cortex. On the contrary, the suprachiasmatic nucleus was very active during the day and relatively inactive during the night as previously reported in the rat.
Animals↗
Evidence for synenkephalin-like immunoreactivity in pontobulbar monoaminergic neurons of the cat.
Using indirect immunofluorescence, evidence that enkephalin- and synenkephalin-like-immunoreactivities are colocalized within numerous monoaminergic neurons of the cat pontobulbar formation is presented. The colocalization concerns most catecholaminergic cell bodies in the locus coeruleus region and numerous serotoninergic cell bodies in the raphe nuclei. Synenkephalin is the 1-70 N-terminal region of the bovine adrenal medulla proenkephalin. Therefore, the proenkephalin (or a related) system seems to represent the biosynthetic pathway for the enkephalins immunodetected within these monoaminergic neurons.
Animals↗
Adrenergic neurons in human brain demonstrated by immunohistochemistry with antibodies to phenylethanolamine-N-methyltransferase (PNMT): discovery of a new group in the nucleus tractus solitarius.
Adrenaline neurons in human brain were demonstrated by immunohistochemistry using antibody to phenylethanolamine-N-methyltransferase (PNMT), the final enzyme in the pathway of adrenaline synthesis, using fixed frozen sections and a highly sensitive free floating technique which utilizes metallization. Small densely packed PNMT-immunoreactive neurons were observed to form a nucleus lying just ventrolateral to the area postrema and in the dorsal part of the nucleus tractus solitarius. Larger adrenergic neurons were also present in and around the lateral reticular nucleus and in relationship with the dorsal motor nucleus of the vagus in regions equivalent to the C1 and C2 groups in rats. Longitudinally oriented PNMT-positive axons constitute a subset of tyrosine hydroxylase-immunoreactive axons in the dorsomedial reticular formation.
Adrenergic Fibers↗