PubMed Health⌕ Search

Biomedical subjects

J Adrien

Publications and source records attributed to J Adrien.

At least 55 records · Page 3Linked to original sources

Alterations of central serotonin and dopamine turnover in rats treated with ipsapirone and other 5-hydroxytryptamine1A agonists with potential anxiolytic properties.

Measurements of tissue levels of monoamines and their metabolites, and of the rates of 5-hydroxytryptophan and dihydroxy-phenylalanine accumulation after blockade of aromatic amino acid decarboxylase by benserazid indicated that ipsapirone (1-10 mg/kg i.p.) decreased 5-hydroxytryptamine (5-HT) turnover and accelerated dopamine (DA) turnover in various brain regions. The reduced 5-HT turnover probably resulted from the stimulation of 5-HT1A autoreceptors within the anterior raphe nuclei as in vitro tests [( 3H]-8-hydroxy-2-[di-n-propylamino]tetralin binding and adenylate cyclase assays) demonstrated that ipsapirone was a 5-HT1A agonist almost as potent as 8-OH-DPAT, and the same decrease in 5-hydroxytryptophan accumulation could be induced by the i.p. (5 mg/kg) or intraraphe (1 microgram) injection of ipsapirone. Ipsapirone-induced acceleration of DA turnover persisted after the selective degeneration of serotoninergic neurons by intraraphe 5,7-dihydroxytryptamine infusion, and could be reproduced by i.p. administration of other 5-HT1A agonists like buspirone and gepirone, but not 8-OH-DPAT. These results demonstrate that ipsapirone-induced acceleration of DA turnover did not result from the stimulation of 5-HT1A (auto)receptors, but involved additional target(s) of the drug. The possible participation of dopaminergic systems in the "anxiolytic" properties of ipsapirone should deserve further investigations.

Animals↗

Lesion of the ponto-geniculo-occipital pathways in kittens. I. Effects on sleep and on unitary discharge of the lateral geniculate nucleus.

Suppression of geniculate ponto-geniculo-occipital (PGO) waves was achieved in kittens by performing bilateral mesencephalic lesions of the PGO pathways. Sleep-wake parameters and the spontaneous unit activity in the lateral geniculate nucleus (LGN) were then chronically recorded during one month after the lesions. Whereas the states of vigilance remained normal, a significant reduction of the unitary discharge in the LGN during paradoxical sleep (PS) and particularly of its phasic component, was observed concomitantly with the suppression of PGO waves. It is concluded that phasic discharge of LGN neurons during PS is controlled by PGO-related mechanisms and that its suppression during the developmental period provides a model for studying its significance on brain maturation.

Animals↗

[What future is there for hydrocephalus children? Intellectual and visual neurological prognosis in series of 77 cases of non-tumor hydrocephalus].

We report the neurological, intellectual and visual outcome of 77 children with hydrocephalus of non tumoral origin. Neurological deficits and epilepsy were common, particularly in those with severe intellectual deficit and with acquired brain damages. Intellectual level prognosis was usually good, although lower than in a healthy population: 75% of children had full intellectual quotient (FIQ) higher than 70 but often, there was an heterogeneous pattern of the IQ with greater differences between verbal and performance results because of poor visual-spatial skills. Attention and syntax comprehension of language disabilities were also specifically encountered. Meningitis or toxoplasmosis secondary to hydrocephalus often resulted in a poor intelligence level but other causes did not influence intelligence level or pattern. Visual-spatial deficits, attention disorders and language disabilities did not seem related to the degree of hydrocephalus or the delay before shunting, but were especially encountered when ventricular dilatation persisted in spite of the operation. Functional amblyopias were frequent, certainly related to strabismus. Optic atrophy was rare and linked to direct compression of the optic nerves or to major and repeated episodes of intracranial hypertension.

Child↗

Ontogenesis of unit activity in the raphe dorsalis of the behaving kitten: its relationship with the states of vigilance.

The relationship between the spontaneous unit activity in the raphe dorsalis (RD), and the sleep-wakefulness cycles, was analyzed in the cat from birth to 40 days of age. Electrodes for polygraphic sleep monitoring were implanted under anesthesia, and unit recordings were obtained from bundles of microwires positioned in the RD area in kittens of different ages. Attention was paid only to units with slow firing in wakefulness (W) (1-6 spikes/s), and two types of discharge patterns during this state were obtained: a 'regular' type, whose discharge in W had the same characteristics of regularity as those described for the adult under the same conditions, was always found inside the RD. An 'irregular' type was always found in sites outside the RD. Injections of different doses of 5-methoxy-N,N-dimethyltryptamine (5-MeODMT i.m.) induced a transient decrease in the firing rate of the regular type of cells, and no change for the units of the irregular type, suggesting that the regular neurons were of serotoninergic nature. Whereas the cells of the irregular type exhibited an increase of discharge frequency in active or paradoxical sleep (AS-PS), those which fired in a clock-like manner during W exhibited a rate of discharge which progressively decreased in quiet or slow wave sleep (QS-SWS) and even more in AS-PS. Such a pattern was qualitatively close to the adult one at all ages, but the discharge rate in AS was significantly higher during the first and second weeks of life than later on. The observation that these serotoninergic neurons exhibited at birth an adult-like pattern of discharge during W, indicates that during ontogenesis there was no direct relationship between the RD activity and the behavioral output. It is proposed that the RD neuronal discharge would be largely under genetic influences, and that the maturation of sleep regulations at the brainstem and mesencephalic levels is achieved only after the second week of postnatal age.

Action Potentials↗

Beta 1 and beta 2 adrenergic receptors: their role in the regulation of paradoxical sleep in the rat.

The influences of beta adrenergic transmission on the regulation of paradoxical sleep (PS) were analysed in the rat. Pharmacological experiments have used beta 1,2 as well as preferential beta 1 or beta 2 compounds. The blockade of the beta 1 adrenoceptors induced a dose-related PS decrease, and stimulation of these preblocked receptors prevented this PS insomnia. SWS was generally not affected. It is concluded that beta 1 neurotransmission is directly involved in the regulation of PS.

Acebutolol↗

Developmental changes in the cerebellar cortex after locus ceruleus lesion with 6-hydroxydopamine in the rat.

Three-day-old rats received an infusion of a small dose of 6-hydroxydopamine (6-OHDA) (12 micrograms) directly into the locus ceruleus nuclei, in order to induce a subtotal lesion of the noradrenergic system. Significant modifications in cerebellum maturation were observed, mainly a regression failure in the perisomatic Purkinje cell processes in the depth of the fissura prima of 10-day-old rats, a reduction in the whole vermis surface area and in the total number of internal granule cells at 15 days of age, the number of external granule cells was slightly enhanced. To discriminate between the effects of the noradrenergic deafferentation and the nonspecific toxic effects of 6-OHDA, these results were compared to those obtained after an infusion of 6-OHDA + bovine serum albumin (BSA) into the locus ceruleus (which produced a selective deafferentation) and after an injection of 6-OHDA directly into the IVth ventricle (which increased the nonspecific toxic effects). Whatever the procedure used, the same reduction in the size of the vermis was observed. However, the fissuration index was not modified when BSA was added to the 6-OHDA solution. We conclude that noradrenergic deafferentation by itself was sufficient to reduce the growth of the cerebellum at certain periods of postnatal life.

Animals↗

Noradrenaline and functional plasticity in kitten visual cortex: a re-examination.

A quantitative re-examination was made of the influence of noradrenergic depletion on the epigenesis of kitten visual cortex. Two methods were used to deplete noradrenaline at the cortical level: stereotaxically controlled injection of 6-hydroxydopamine (6-OHDA) in the coeruleus complex, from which the noradrenergic input to visual cortex arises; intraventricular injection of 6-OHDA. The latter chemical lesion also depleted dopamine levels in the brain. Lesion of the noradrenergic or catecholaminergic systems was performed neonatally or at an age of 3-4 weeks in kittens submitted to five different rearing procedures: normal rearing, dark rearing, monocular rearing, monocular exposure following dark rearing and monocular deprivation following normal rearing. Forty-two kittens between 3 and 12 weeks of age were used for this biochemical and electrophysiological study. Noradrenaline and dopamine levels were measured by a radioenzymatic method in the primary visual cortex of twenty-six kittens. A total of 1263 cells were recorded in area 17 of twenty-six kittens. Combined biochemical and electrophysiological data were obtained in ten 6-OHDA-lesioned kittens. Whatever the mode of chemical lesion used, cortical noradrenergic depletion failed to block either maturation or vision-dependent processes which are known to affect orientation selectivity and/or ocular dominance during the critical period. However, in some cases, the amplitude of the epigenetic functional modifications was slightly reduced in 6-OHDA-treated kittens. The cortical effects of monocular deprivation starting from the age of 5 weeks were studied quantitatively both in lesioned and intact kittens. Disappearance of noradrenaline in area 17 did not prevent the loss of binocularity in cortical cells. However, even when monocular occlusion had been maintained for 2 or 3 weeks in 6-OHDA-treated kittens, ocular dominance shifts were limited to a stage equivalent to that observed in the intact kitten after 5-8 days of monocular occlusion. The amplitude of this partial protective effect was found to be unrelated either to the delay following the chemical lesion, or to the level of noradrenaline remaining in lesioned kitten cortex. Although a putative gating role of noradrenaline cannot be excluded in the development of the intact animal, this report shows that its presence is not required for functional plasticity to occur in kitten area 17.

Animals↗

[Electrophysiological maturation of neurons of the lateral geniculate nucleus after lesion of ponto-geniculo-occipital pathways in kittens].

Bilateral mesencephalic lesions, which suppress the PGO activity in the lateral geniculate nucleus (LGN), were performed at two weeks of age in the kitten, and the effects on the electrophysiological development of this nucleus were analyzed at 6 weeks of age. The latencies of LGN cells after electrical stimulation of the optic chiasma were larger, and the number of the differentiated X cells was smaller than those of age paired controls. However, the response of the ganglion fibers was not modified. These results, compared to those obtained on 30 days old kittens, and on animals with a unilateral lesion, suggest that the suppression of PGO inputs to the LGN induced a delay in the electrophysiological maturation of this nucleus.

Animals↗

[Induction of paradoxical sleep (PS) by infusion of cerebrospinal fluid from PS-deprived rats].

In the rat, alpha-Methyldopa (alpha-MD, 50 mg/kg i.p.) induced during 8 hrs. an important reduction of paradoxical sleep (PS) and an increase of light slow waves sleep (SWS1). These effects were reversed by intraventricular infusion of cerebrospinal fluid (CSF) from PS-deprived donor rats, and PS restauration depended directly on the duration of the deprivation in the donor. It is probable that hypnogenic substances accumulate in the CSF during PS-deprivation, and that these factors can by-pass the noradrenergic step in the chain of biochemical events normally leading to the appearance of PS.

Animals↗

Presence of a paradoxical sleep (PS) factor in the cerebrospinal fluid of PS-deprived rats.

The lack of paradoxical sleep (PS) observed in rats after pharmacological blockade of the noradrenergic beta-receptors was reversed by intraventricular infusion of cerebrospinal fluid (CSF) from PS-deprived donor rats. The PS restoration in recipient animals was proportional to the duration of the deprivation in donors. It is concluded that some PS-inducing factor progressively accumulates in the CSF during deprivation. This factor acts beyond the noradrenergic step in the regulation of PS.

Animals↗

Suppression of PGO waves in the kitten: anatomical effects on the lateral geniculate nucleus.

Bilateral mesencephalic electrolytic lesions were performed in 2-week-old kittens, in order to suppress the ascending ponto-geniculo-occipital activity. The subsequent anatomical development of the lateral geniculate nucleus was analyzed. A significant maturational deficit was evidenced in 5-week-old experimental kittens as compared to age-paired controls. It is concluded that a lesion in the X area impairs the maturation of CNS. The relationship between this area (the phasic components of paradoxical sleep) and the maturation of CNS are still to be demonstrated.

Animals↗

[Beta-adrenergic influences on the firing of raphe dorsalis neurons after neonatal noradrenergic deafferentation in the rat].

In Rat, neonatal lesion of the locus coeruleus induces modifications of beta-adrenergic regulations at the level of raphe dorsalis neurons. In normal conditions, the firing of serotoninergic raphe cells is not beta-adrenergic dependent. On the contrary in the lesioned animal, iontophoresis of a beta-blocking agent (DL-propranolol) produces a marked inhibition of the serotoninergic unit firing. Various mechanisms may account for this pharmacological response in the lesioned group: a classical hypersensitivity phenomenon, or the persistence of an immature regulation.

Afferent Pathways↗

[Noradrenaline and plasticity of the visual cortex of the kitten: a reexamination].

We have undertaken a study of the role of the noradrenergic system in the functional modifications, observed in the primary visual cortex of the Kitten, following monocular deprivation. The lids of one eye were sutured in 5 week old Kittens for a period of 1 or 2 weeks. Noradrenergic depletion was obtained by 6-OHDA injection, either intraventricular or localized in the coeruleus complex. Our results indicate that disappearance of noradrenaline in area 17 does not prevent the loss of binocularity of cortical cells, but appears to limit ocular dominance shifts at a stage equivalent to that observed in the intact Kitten after 6 days of monocular deprivation.

Animals↗

Regulation of sleep after neonatal locus coeruleus lesion: functional evidence of beta-adrenergic supersensitivity.

In the present report we analyzed the long-term effect of neonatal noradrenergic denervation on the regulation of paradoxical sleep in the rat. The locus coeruleus was destroyed bilaterally at 4 days of age by direct infusion of 6-hydroxydopamine into the nuclei. After they reached adulthood, the rats received either i.p. injections of a beta-blocker, propranolol, or the same treatment combined with intraventricular infusion of a beta-agonist, isoproterenol. Several doses of each drug were tested. The effects of propranolol, alone and together with isoproterenol, on paradoxical sleep (a decrease for the former drug and a restoration for the latter combination) were significantly more pronounced in the lesioned group than in age-paired controls. These data illustrate a functional aspect of the denervation supersensitivity phenomenon in beta-receptors.

Adrenergic beta-Antagonists↗

Septal driving of hippocampal theta rhythm as a function of frequency in the infant male rat.

The threshold current of septal stimulation required to drive the hippocampal theta rhythm was investigated as a function of stimulation frequency in male rats aged 12-19 days. The minimum in the threshold-frequency function at 7.7 Hz, characteristic of adult male rats, appeared at 15-16 days. Before that age the relation between frequency and threshold was monotonic, as in adult female rats.

Animals↗

Development of the dopaminergic innervation of the rat cerebral cortex. A light microscopic immunocytochemical study using anti-tyrosine hydroxylase antibodies.

A precise topographical analysis of the distribution of tyrosine hydroxylase-like immunoreactive processes was performed in the frontal, cingular and parietal cortex of the rat during late embryonic and early postnatal life. Until birth, labeled processes were only observed in the restricted cortical areas known to receive a dopaminergic innervation in the adult brain. Their distribution differed markedly from that of noradrenergic fibers as identified by their dopamine-beta-hydroxylase-like immunoreactivity. Thus we considered TH-like immunoreactivity to be a selective marker of the cortical dopaminergic innervation during late fetal life, at least with the antibody we used. With this marker, dopaminergic fibers were first detected in the anterior frontal cortex at day 16 of embryonic life (E16). They developed as two bundles passing medially and laterally to the ventricular layer without penetrating it. From E20 on, the terminal fields extended to the cingular and rhinal cortex, still being restricted to the intermediate zone. No fibers were visible in the lateral and dorsal frontal cortex at this time, nor in the cortical plate and molecular layer in any cortical area. At E21, rare labeled fibers were seen in the molecular layer of the medial frontal and cingular cortex. After birth, the terminal fields of the TH-containing fibers extended further caudally in the cingular cortex and also superficially in the cortical plate. Moreover, labeled axons now also appeared in the lateral frontal and parietal cortex where their density gradually increased. At P14, two different patterns of distribution were observed: a high density of TH-positive fibers in the cortical areas known to receive a dopaminergic innervation; a low density of fibers in the other cortical areas which represented noradrenergic fibers. Indeed these TH-containing presumed noradrenergic fibers were absent at P14 following a bilateral destruction of the locus coeruleus in 4-day-old pups.

Animals↗

Destruction of noradrenergic cell bodies by intracerebral 6-hydroxydopamine in the newborn rat.

Intracerebral injections of 6-hydroxydopamine directly in the nucleus locus coeruleus were performed in 4-day-old rats. The effects of such treatment on the subsequent development of this nucleus were analyzed and compared to those obtained in vehicle-injected age-paired controls. The 3 histological techniques used (Nissl, Glenner reaction, and histochemical fluorescence) indicated in the experimental group a progressive disappearance of the coerulean perikarya within 7 days postinjection. This lesion was permanent and did not induce any noradrenergic sprouting.

Animals↗

[Beta-adrenergic receptors and paradoxical sleep in the rat].

Treatment of adult rats with a beta-adrenergic blocking agent (propranolol) induced a paradoxical sleep deficit which was dose-related. This deficit could be completely corrected by intraventricular perfusion with a beta-agonist (isoproterenol), according to a dose-dependent function. The beta-adrenergic receptors may therefore be specifically involved in the regulation of paradoxical sleep.

Animals↗