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M Jouvet

Publications and source records attributed to M Jouvet.

At least 19 recordsLinked to original sources

Cholinergic neurons with monoamine oxidase type B (MAOB)-activity in the laterodorsal tegmental nucleus of the mouse.

No neurons in the laterodorsal tegmental nucleus (LDTg) show monoamine oxidase (MAO) activity in the rat or monkey. However, in our recent study, many LDTg neurons with MAO type B (MAOB)-activity were found in MAOA-deficient mice that were derived from C3H mouse line. In the present study, LDTg neurons with MAOB-activity were found not only in normal C3H mouse but also in BALB/C and C57BL/6 mouse lines: MAO histochemistry revealed LDTg neurons with MAO-activity even after pharmacological suppression of MAOA-activity with clorgyline, a specific MAOA inhibitor, but not after pharmacological suppression of MAOB-activity with deprenyl, a specific MAOB inhibitor. LDTg neurons with MAOB-activity also showed NADPH-diaphorase-activity, a marker of cholinergic neurons.

Animals

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

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

Sleep and serotonin: an unfinished story.

Serotonin (5-HT) was first believed to be a true neuromodulator of sleep because the destruction of 5-HT neurons of the raphe system or the inhibition of 5-HT synthesis with p-chlorophenylalanine induced a severe insomnia which could be reversed by restoring 5-HT synthesis. However the demonstration that the electrical activity of 5-HT perikarya and the release of 5-HT are increased during waking and decreased during sleep was in direct contradiction to this hypothesis. More recent experiments suggest that the release of 5-HT during waking may initiate a cascade of genomic events in some hypnogenic neurons located in the preoptic area. Thus, when 5-HT is released during waking, it leads to an homeostatic regulation of slow-wave sleep.

Animals

Hyperoxia increases paradoxical sleep rhythm in the pontine cat.

Pontine cat is an ectothermic preparation, whose central temperature can artificially be lowered from 36 degrees C to 26 degrees C; this gradual hypothermia is accompanied by a dramatic increase in paradoxical sleep (PS). Two main hypotheses might explain this result: executive systems of PS might be switched on gradually by cold-sensitive thermodetectors, whereas inhibitory monoaminergic mechanisms appear to be warm-sensitive. On the other hand, energy saving mechanisms peculiar to hypothermia might promote PS appearance. Indeed, in normal animals, PS is selectively suppressed both by hyperthermia and hypoxia. The inhibitory effect of hypoxia might explain why hypothermia, which protects the brain against hypoxic alterations, might facilitate PS. If this last hypothesis is correct, the putative increase in cerebral oxygen supply might increase PS. For this reason, we submitted eight pontine carotid-deafferented cats, kept at the same central temperature (34 +/- 0.5 degrees C: temperature clamp) to periodic hyperoxia (PaO2 = 58 +/- 7 kPa) or room air (PaO2 = 17 +/- 2 kPa) alternatively during 4- or 12-h periods. Hyperoxia induced an 85% increase in PS, mainly due to an increase in PS rhythm (PS cycle duration was 65 +/- 4 min in normoxia and 45 +/- 4 min in hyperoxia, p<0.0001). In five animals, after hyperoxia, PS cycle returned gradually back to control values in 4 to 12 h. These findings show that PS is exquisitely sensitive to conditions that impair oxidative metabolism. The role of cholinergic executive PS systems as putative metabolic-sensitive neurons remains to be established.

Activity Cycles

Forebrain afferents to the rat dorsal raphe nucleus demonstrated by retrograde and anterograde tracing methods.

The dorsal raphe nucleus through its extensive efferents has been implicated in a great variety of physiological and behavioural functions. However, little is know about its afferents. Therefore, to identify the systems likely to influence the activity of serotonergic neurons of the dorsal raphe nucleus, we re-examined the forebrain afferents to the dorsal raphe nucleus using cholera toxin b subunit and Phaseolus vulgaris-leucoagglutinin as retrograde or anterograde tracers. With small cholera toxin b subunit injection sites, we further determined the specific afferents to the ventral and dorsal parts of the central dorsal raphe nucleus, the rostral dorsal raphe nucleus and the lateral wings. In agreement with previous studies, we observed a large number of retrogradely-labelled cells in the lateral habenula following injections in all subdivisions of the dorsal raphe nucleus. In addition, depending on the subdivision of the dorsal raphe nucleus injected, we observed a small to large number of retrogradely-labelled cells in the orbital, cingulate, infralimbic, dorsal peduncular, and insular cortice, a moderate or substantial number in the ventral pallidum and a small to substantial number in the claustrum. In addition, we observed a substantial to large number of cells in the medial and lateral preoptic areas and the medial preoptic nucleus after cholera toxin b subunit injections in the dorsal raphe nucleus excepting for those located in the ventral part of the central dorsal raphe nucleus, after which we found a moderate number of retrogradely-labelled cells. Following cholera toxin b subunit injections in the dorsal part of the central dorsal raphe nucleus, a large number of retrogradely-labelled cells was seen in the lateral, ventral and medial parts of the bed nucleus of the stria terminalis whereas only a small to moderate number was visualized after injections in the other dorsal raphe nucleus subdivisions. In addition, respectively, a substantial and a moderate number of retrogradely-labelled cells was distributed in the zona incerta and the subincertal nucleus following all tracer injections in the dorsal raphe nucleus. A large number of retrogradely-labelled cells was also visualized in the lateral, dorsal and posterior hypothalamic areas and the perifornical nucleus after cholera toxin b subunit injections in the dorsal part of the central raphe nucleus and to a lesser extent following injections in the other subdivisions. We further observed a substantial to large number of retrogradely-labelled cells in the tuber cinereum and the medial tuberal nucleus following cholera toxin b subunit injections in the dorsal part of the central dorsal raphe nucleus or the lateral wings and a small to moderate number after injections in the two other dorsal raphe nucleus subdivisions. A moderate or substantial number of labelled cells was also seen in the ventromedial hypothalamic area and the arcuate nucleus following cholera toxin injections in the dorsal part of the central dorsal raphe nucleus and the lateral wings and an occasional or small number with injection sites located in the other subdivisions. Finally, we observed, respectively, a moderate and a substantial number of retrogradely-labelled cells in the central nucleus of the amygdala following tracer injections in the ventral or dorsal parts of the central dorsal raphe nucleus and a small number after injections in the other subnuclei. In agreement with these retrograde data, we visualized anterogradely-labelled fibres heterogeneously distributed in the dorsal raphe nucleus following Phaseolus vulgaris-leucoagglutinin injections in the lateral orbital or infralimbic cortice, the lateral preoptic area, the perifornical nucleus, the lateral or posterior hypothalamic areas, the zona incerta, the subincertal nucleus or the medial tuberal nucleus. (ABSTRACT TRUNCATED)

Animals

Paradoxical sleep as a programming system.

The concept of 'psychological individuation' i.e 'intraspecific variability' is essential for evolution as stated by Mayr (1958). It has been recently revived by the study of Bouchard (1990) in homozygous twins separated at birth and reared in different environments. These twins still retain identical psychological idiosyncratic reactions. Even if their brains are almost identical at birth, it is most likely that the different epigenetic stimuli from the external world have differently altered many cerebral synaptic circuitry due to the plasticity of the brain. Therefore, in order to maintain an identical psychological profile, there should be a mechanism which would reinforce the genetic programmation of the central nervous system either in reinforcing or erasing special genetic circuitry which would be stimulated during previous and/or subsequent waking periods. In ectothermic vertebrates, in immature mammals or sometimes in mature birds, this programming can be effectuated by neurogenesis. After neurogenesis has stopped in mammals, paradoxical sleep would be well suited for reinforcing the genetic programming during sleep. The patterns of portogeniculo-occipital (PGO) activity (which depend upon genetic factors) would be responsible for this function, together with the theta activity of the hippocampus (read out of previous waking events) and fast cortical EEG. This programming would activate all the brain including the pyramidal motor system while movements would be suppressed by the system controlling muscle atonia.

Brain

Neurochemical and behavioral effects of ciproxifan, a potent histamine H3-receptor antagonist.

Ciproxifan, i.e., cyclopropyl-(4-(3-1H-imidazol-4-yl)propyloxy) phenyl) ketone, belongs to a novel chemical series of histamine H3-receptor antagonists. In vitro, it behaved as a competitive antagonist at the H3 autoreceptor controlling [3H]histamine release from synaptosomes and displayed similar Ki values (0.5-1.9 nM) at the H3 receptor controlling the electrically-induced contraction of guinea pig ileum or at the brain H3 receptor labeled with [125I]iodoproxyfan. Ciproxifan displayed at least 3-orders of magnitude lower potency at various aminergic receptors studied in functional or binding tests. In vivo, measurement of drug plasma levels, using a novel radioreceptor assay in mice receiving ciproxifan p.o. or i.v., led to an oral bioavailability ratio of 62%. Oral administration of ciproxifan to mice enhanced by approximately 100% histamine turnover rate and steady state level of tele-methylhistamine with an ED50 of 0.14 mg/kg. Ciproxifan reversed the H3-receptor agonist induced enhancement of water consumption in rats with and ID50 of 0.09 +/- 0.04 mg/kg, i.p. In cats, ciproxifan (0.15-2 mg/kg, p.o.) induced marked signs of neocortical electroencephalogram activation manifested by enhanced fast-rhythms density and an almost total waking state. In rats, ciproxifan enhanced attention as evaluated in the five-choice task performed using a short stimulus duration. Ciproxifan appears to be an orally bioavailable, extremely potent and selective H3-receptor antagonist whose vigilance- and attention-promoting effects are promising for therapeutic applications in aging disorders.

Animals

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

Preferential expression of kin, a nuclear protein binding to curved DNA, in the neurons of the adult rat.

The KIN17 gene product has been identified by cross immunoreactivity with anti-RecA antibodies and by DNA recombination techniques, and is probably part of the DNA recombination-repair machinery. Following Western blotting and immunocytochemistry using anti-RecA antibodies, and in situ hybridization with specific KIN17 cDNA probes, we here report the detection of high levels of KIN protein and KIN17 mRNA in the CNS of adult rats. The RecA cross-reacting protein has an apparent molecular weight of 41 kDa and is located in the nucleus of brain cells. Both the KIN17 transcript and the protein were found to be widespread, but they were present in different proportions, depending on the type of brain cells. High levels of KIN protein were seen in neurons of the motor nuclei of the brainstem, the locus coeruleus, hippocampal formation, entorhinal cortex, Purkinje cells, pyramidal cells of the cortex and mitral cells. In contrast, using a combination of KIN17 mRNA in situ hybridization and GFAP immunocytochemistry (a marker of glial cells) showed that the KIN17 messenger is preferentially transcribed in neurons, the post-mitotic and long lived brain cells. We postulate that KIN17 play a role in the illegitimate recombination of DNA sequences and/or the repair of alterations of the genome in neurons.

Age Factors

Transgene expression of plasmid DNAs directed by viral or neural promoters in the rat brain.

The use of circular plasmid DNA may be an alternative method for the transfer of genes into the brain and is presumably easier to use than other vectors, such as viruses or genetically engineered cells. The effectiveness and time course of the expression of a reporter gene (LacZ), directed by appropriate promoters, was studied after stereotaxic injection of naked plasmid DNAs into the rat thalamus, cortex or cerebellum. The efficiencies of three different promoters, the human cytomegalovirus (HCMV) promoter and the glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE) promoters (specific for astrocytes and neurons, respectively) to drive reporter gene expression were compared. Efficient expression of beta-gal, detected by X-gal histochemistry or immunochemistry, required the use of 50 microg of DNA and was detectable as early as 48 h after injection. Expression increased until day 8, remained stable until day 15, then decreased over 2 months, probably as a result of non-specific degradation of the plasmids within the transfected cells rather than from specific down-regulation of promoters, as the same time course was seen with all three promoters tested. Depending on the promoter used (GFAP or NSE), LacZ was preferentially expressed within astrocytes or neurons, respectively. The GFAP promoter was found to be as efficient as the HCMV promoter, possibly due to the reactive gliosis induced by plasmid injection which is known to up-regulate GFAP expression.

Animals

Determination of NADH in the rat brain during sleep-wake states with an optic fibre sensor and time-resolved fluorescence procedures.

The present paper reports a nanosecond time-resolved fluorescence derived from the cortex and the area of the periaqueductal gray including the nucleus raphe dorsalis (PAG-nRD) in unanaesthetized freely moving rats. The measurements were acquired through a single optic fibre transmitting a subnanosecond nitrogen laser pulse (337 nm, 15 Hz) and collecting the brain fluorescence occurring at 460 nm which might depend on mitochondrial NADH (reduced form of nicotinamide adenine dinucleotide). The fluorometric method was combined with polygraphic recordings, and this procedure allowed us to define, for the first time, variations of the 460 nm signal occurring throughout the sleep-wake cycle. In the PAG-nRD, the signal exhibited moderate heterogeneous variation in amplitude during slow-wave as compared to the waking state. Constant increases were observed during paradoxical sleep as compared to the waking state. For this state of sleep the magnitude of the variations depended on the optic fibre location. In the cortex and during either slow-wave sleep or paradoxical sleep, the signal presented moderate increases which were significant during paradoxical sleep. The magnitude of the redox variations observed either in the PAG-nRD or in the cortex might be ascribed to the oxidative energy balance which is related to sleep states.

Animals

Afferent projections to the rat nuclei raphe magnus, raphe pallidus and reticularis gigantocellularis pars alpha demonstrated by iontophoretic application of choleratoxin (subunit b).

The aim of the present study was to identify the specific afferent projections to the rostral and caudal nucleus raphe magnus, the gigantocellular reticular nucleus pars alpha and the rostral nucleus raphe pallidus. For this purpose, small iontophoretic injections of the sensitive retrograde tracer choleratoxin (subunit b) were made in each of these structures. In agreement with previous retrograde studies, after all injection sites, a substantial to large number of labeled neurons were observed in the dorsal hypothalamic area and dorsolateral and ventrolateral parts of the periaqueductal gray, and a small to moderate number were found in the lateral preoptic area, bed nucleus of the stria terminalis, paraventricular hypothalamic nucleus, central nucleus of the amygdala, lateral hypothalamic area, parafascicular area, parabrachial nuclei, subcoeruleus area and parvocellular reticular nucleus. In addition, depending on the nucleus injected, we observed a variable number of retrogradely labeled cells in other regions. After injections in the rostral nucleus raphe magnus, a large number of labeled cells were seen in the prelimbic, infralimbic, medial and lateral precentral cortices and the dorsal part of the periaqueductal gray. In contrast, after injections in the other nuclei, fewer cells were localized in these structures. Following raphe pallidus injections, a substantial to large number of labeled cells were observed in the medial preoptic area, median preoptic nucleus, ventromedial part of the periaqueductal gray, Kölliker-Fuse and lateral paragigantocellular reticular nuclei. Following injections in the other areas, a small to moderate number of cells appeared. After gigantocellular reticular pars alpha injections, a very large and substantial number of labeled neurons were found in the deep mesencephalic reticular formation and oral pontine reticular nucleus, respectively. After the other injections, fewer cells were seen. Following rostral raphe magnus or raphe pallidus injections, a substantial number of labeled cells were observed in the insular and perirhinal cortices. Following caudal raphe magnus or gigantocellular reticular pars alpha injections, fewer cells were found. After raphe magnus or gigantocellular reticular pars alpha injections, a moderate to substantial number of cells were localized in the fields of Forel, lateral habenular nucleus and ventral caudal pontine reticular nucleus. Following raphe pallidus injections, only a small number of cells were seen. Our data indicate that the rostral and caudal parts of the nucleus raphe magnus, the gigantocellular reticular nucleus pars alpha and the nucleus raphe pallidus receive afferents of comparable strength from a large number of structures. In addition, a number of other afferents give rise to stronger inputs to one or two of the four nuclei studied. Such differential inputs might be directed to populations of neurons with different physiological roles previously recorded specifically in these nuclei.

Afferent Pathways

Potential brain neuronal targets for amphetamine-, methylphenidate-, and modafinil-induced wakefulness, evidenced by c-fos immunocytochemistry in the cat.

Much experimental and clinical data suggest that the pharmacological profile of modafinil, a newly discovered waking substance, differs from those of amphetamine and methylphenidate, two classical psychostimulants. The brain targets on which modafinil acts to induce wakefulness, however, remain unknown. A double-blind study using the protooncogene c-fos as experimental marker in the cat was, therefore, carried out to identify the potential target neurons of modafinil and compare them with those for amphetamine and methylphenidate. Cats were sacrificed after a single oral administration of amphetamine, methylphenidate, or modafinil at equivalent doses for wake induction (1, 2.5, or 5 mg/kg, respectively) and brain sections examined for Fos by immunocytochemistry. Administration of either amphetamine or methylphenidate evoked Fos-like immunoreactivity in a large number of neurons in the striatum and whole cortex, especially in the caudate nucleus and mediofrontal cortex, which are known to be dopaminergic targets. In contrast, administration of modafinil resulted in the labeling of few cells in these structures, but did induce marked Fos labeling in neurons of the anterior hypothalamic nucleus and adjacent areas. These results provide evidence for the potential brain targets of modafinil, which differ from those of amphetamine or methylphenidate, and suggest that modafinil induces wakefulness by mechanisms distinct from those of the two stimulants.

Amphetamine

Effects of tianeptine, sertraline and clomipramine on brain serotonin metabolism: a voltammetric approach in the rat.

Tianeptine is a substance enhancing the serotonir uptake while sertraline and clomipramine inhibit it. By means of 5-hydroxyin-doleacetic acid (5-HIAA) voltammetric measurements, this study investigated their influence on serotonin metabolism which depends mainly upon the activity of monoamine oxidase type A. After tianeptine injection the 5-HIAA signal increased by about 60%. This effect was maintained when the animals were pre-treated with MDL 72145 (an inhibitor of monoamine oxidase type B) but reduced when clorgyline (an inhibitor of monoamine oxidase type A) was administered after tianeptine. Administration of sertraline or clomipramine reduced the 5-HIAA signal by about 30-50%, whether the animals were pre-treated with MDL 72145 or not. It is to be concluded that tianeptine, sertraline and clomipramine can regulate the 5-HT fraction present in the synaptic cleft, not only by acting at the level of the serotoninergic neurons, but also by favoring or reducing the access of the amine to monoamine oxidase type A which is synthesized within non-serotoninergic neurons and glial cells.

1-Naphthylamine

Forebrain projections of the rostral nucleus raphe magnus shown by iontophoretic application of choleratoxin b in rats.

The nucleus raphe magnus belongs to the thermoafferent system. Following iontophoretic choleratoxin b injections in its rostral part, a substantial to large number of anterogradely labeled varicose fibres were observed in the medial and lateral preoptic areas, the bed nucleus, the substantia innominata, the ventral pallidum, the median preoptic nucleus, the paraventricular hypothalamic nucleus, the central amygdaloid nucleus and the lateral and dorsal hypothalamic areas. A small to moderate number were seen in the septal nuclei, the diagonal band, the magnocellular preoptic nucleus, the anterior hypothalamic area and the paraventricular and intralaminar thalamic nuclei. After choleratoxin b injections in the preoptic, dorsal and lateral hypothalamic areas, a substantial number of retrogradely labeled serotonin immunonegative neurones were specifically found in the rostral nucleus raphe magnus. Thus, non-serotonergic rostral nucleus raphe magnus cells might directly modulate hypothalamic thermointegrative neurones.

Afferent Pathways

Alterations in c-fos expression after different experimental procedures of sleep deprivation in the cat.

In the present study, we sought to examine the expression of the c-fos proto-oncogene in the cat brain after two different procedures of 24 h sleep deprivation. A first group of cats was gently sleep-deprived; they were awoken by a gentle touch of the hand (n = 5). A second group was sleep-deprived by the water tank technique which is a stressful deprivation (n = 4). A third group was placed 2 h on the water tank and was therefore stressed but not sleep-deprived (n = 2). A fourth group (control group of basal and unspecific Fos expression) was not sleep-deprived (n = 5). These four groups allowed us to separate Fos expression due to stress from Fos expression due to sleep deprivation. On the one hand, compared with controls cats, an important increase in Fos expression, detected by immunohistochemistry, was observed in the preoptic area of sleep-deprived cats by both gentle and stressful methods. On the other hand, there was a significant increase in Fos expression in the lateral hypothalamus of gently deprived cats as compared with control cats. These data indicate that c-fos expression can be employed as a marker of some putative homeostatic mechanism regulating sleep. The only sites in which there was a significant increased number of c-fos expressing neurons were located in the preoptic area which is known to be involved in sleep and in the lateral hypothalamic area.

Animals

Alteration in central and peripheral substance P- and neuropeptide Y-like immunoreactivity after chronic hypoxia in the rat.

The influence of long-term hypoxia on substance P (SP) and neuropeptide Y (NPY)-like immunoreactivity (LI) in discrete brain areas and peripheral structures was assessed by radioimmunoassay. Rats were exposed to normobaric hypoxia (10% O2 in nitrogen) for 14 days. In the carotid bodies of hypoxic animals, NPY-LI was significantly increased (56% vs. normoxic controls) while SP-LI was unchanged. In the brain, NPY-LI was increased in the ventrolateral medulla oblongata (23%) and in the striatum (53%); however, SP-LI was unaltered in these two regions. In the anterior pituitary, NPY-LI was increased (99%), while SP-LI was decreased (37%). No significant alteration in NPY-LI and SP-LI was observed in other discrete brain areas or peripheral structures studied. These results show that, in the rat, long-term hypoxia induces changes in NPY-LI or SP-LI in a few central and peripheral structures; these biochemical alterations may be linked to adaptative mechanisms involving morphological changes in carotid bodies or alterations in sympathetic control and neuroendocrine function.

Adrenal Glands