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Biomedical subjects

S Bourgoin

Publications and source records attributed to S Bourgoin.

At least 127 records · Page 7Linked to original sources
PubMed1982

In vivo modulations by GABA-related drugs of met-enkephalin release in basal ganglia of the cat brain.

The influence of the intrapallidal application of GABA-related compounds on the release of Met-enkephalin in the globus pallidus and the caudate nucleus in the two hemispheres was investigated in vivo in the cat. For this purpose, the 4 structures were continuously superfused with an artificial CSF through implanted push-pull cannulae and Met-enkephalin released in superfusates was determined using a specific radioimmunoassay. GABA (10-500 microM) reduced the local release of Met-enkephalin during its application but once the amino acid was removed from the superfusing fluid, an increase in the peptide release was observed. Diazepam (10 microM) induced only an inhibitory effect whereas muscimol (1 microM) stimulated Met-enkephalin release. Opposite changes in Met-enkephalin release were also seen with the GABA antagonists, bicuculline methiodide (1 microM) and picrotoxin (10 microM), suggesting that the local regulation of Met-enkephalin release by GABA related compounds may be mediated by at least two types of GABA receptors. In several cases, the unilateral pallidal application of GABA agonists and antagonists induced significant changes in Met-enkephalin release at distant structures. The most striking effect was observed with diazepam which markedly reduced the peptide release in both caudate nuclei and pallida. These data suggest that GABAergic systems can contribute to some bilateral regulation of striato-pallidal enkephalinergic neurones.

Animals↗
PubMed1982

Increased levels of Met-enkephalin-like material in the CSF of anaesthetized cats after tooth pulp stimulation.

Tooth pulp stimulation in halothane-anaesthetized cats induced a long lasting (greater than or equal to 3 h) increase in the levels of Met-enkephalin-like material (MELM) in the cisternal CSF. Chromatographic analyses (gel filtration, HPLC) revealed that most of the immunoreactivity was attributable to high molecular weight (mol. wt. greater than or equal to 4000) compounds; in non-stimulated cats, Met-enkephalin (largely in the form of the sulfoxide derivative) only accounted for about 10% of total MELM. In contrast, following tooth pulp stimulation, a large increase in Met-enkephalin (plus Met-Ox5-enkephalin) levels was noted so that the pentapeptide thus represented more than 50% of total MELM. No evidence was obtained for the presence of Met-enkephalin-Arg6-Phe7 in the cisternal CSF of halothane-anaesthetized cats. These data strongly suggest that the activity of enkephalinergic neurons was increased following nociceptive stimulation. This indirectly supports the possible physiological role of enkephalinergic systems in modulating nociceptive inputs.

Animals↗
PubMed1981

Long lasting effects of intrauterine growth retardation of 5-HT metabolism in the brain of developing rats.

Intrauterine growth retardation (IUGR) was achieved by ligating the artery and vein supplying one uterine horn in pregnant rats on the 5th day before delivery. At birth, the weight of the whole body and of the forebrain (but not that of the brain stem of about half of the offspring) were significantly lower than those of normal controls. This deficit persisted for at least the first 3 postnatal weeks. During the immediate period following birth, the concentrations of norepinephrine, dopamine, serotonin and 5-hydroxyindoleacetic acid (5-HIAA) were significantly higher in IUGR rats than in controls. Increased levels of serotonin and 5-HIAA were still observed in the forebrain and brain stem of 15-day-old IUGR rats and were associated with parallel increases in brain and serum free tryptophan levels. These results indicate that a transient insult in the fetal life could result in long-lasting alterations in 5-HT metabolism in CNS of developing rats.

Animals↗
PubMed1981

In vivo evidence for GABAergic control of serotonin release in the cat substantia nigra.

Push-pull cannulae were used for estimating the release of endogenously synthesized [3H]serotonin in both substantia nigra and caudate nuclei of halothane-anaesthetized cats. The unilateral nigral application of GABA (10-5 M) reduced the local release of [3H]serotonin picrotoxin induced an opposite effect. Both treatments failed to modify [3H]serotonin release in the caudate nuclei or in the contralateral substantia nigra. These results suggest that GABAergic neurons innervating the substantia nigra may regulate nigral serotonin transmission. The possibility that such a regulation could be presynaptic (direct or through other nigral neurotransmitters) or related to a change in the activity of the nigro-raphe projection is discussed.

Animals↗
PubMed1981

Kinetic characteristics of newly synthesized 3H-5-HT in the brain of control and reserpinized mice. Evidence for the heterogeneous distribution of 5-HT in serotoninergic neurons.

Following an intravenous administration of 3H-tryptophan to mice, 3H-serotonin rapidly accumulated in the brain, with a maximum around the 20th min after the injection. In mice whole monoamine oxidase activity was blocked by pargyline (75 mg/kg i.p.), reserpine pretreatment (5 mg/kg, 24 h before death) did not alter the initial accumulation of 3H-5-HT indicating that the rate of 5 HT synthesis was similar in control and reserpinized animals. When monoamine oxidase was not blocked, the accumulation of 3H-5-HT was significantly lower in reserpine-treated mice than in controls. However, the specific activity of 3H-5-HT accumulated in brain was 2-3 times higher in reserpinized (45 h) than in control mice. Since neither the specific activity of the precursor 3H-tryptophan, the reuptake process for 3H-5-HT nor the absolute synthesis rate of 5-HT was altered in the brain of reserpinized mice, it is proposed that the differences observed in the specific activity of 3H-5-HT reflected the presence of 3H-5-HT in different compartments in control and reserpinized mice. Serotonin would be distributed in a "storage" and a "functional" compartments in serotoninergic neurons under normal conditions whereas only the functional compartment would exist 18-48 h after the administration of reserpine.

Animals↗
PubMed1981

Long lasting effects of intrauterine malnutrition on neurotransmitters metabolism in the brain of developing rats.

Intrauterine growth retardation (IUGR) was achieved by ligating the artery and vein supplying one uterine horn in pregnant rats on the 5th day before delivery. At birth, the weight of the whole body and of the forebrain (but not that of the brain stem of about half of offspring) were significantly lower than those of normal controls. This deficit persisted for at least the first 3 postnatal weeks. During the immediate period following birth, the concentrations of norepinephrine, dopamine, serotonin and 5-hydroxyindoleacetic acid (5-HIAA) were significantly higher in IUGR rats than in controls. Increased levels of serotonin and 5-HIAA were still observed in the forebrain and brain stem of 15-day-old IUGR rats and were associated with parallel increases in brain and serum free tryptophan levels. These results indicate that a transient insult in the fetal life could result in long-lasting alterations in 5-HT metabolism in the CNS of developing rats.

Animals↗
PubMed1981

The respective roles of tryptophan uptake and tryptophan hydroxylase in the regulation of serotonin synthesis in the central nervous system.

1. The rate limiting enzyme for the synthesis of serotonin (5-HT) in brain, tryptophan hydroxylase, is not saturated under normal physiological conditions. 2. Therefore, any decrease or increase in brain tryptophan levels results in a reduction or a stimulation of 5-HT synthesis respectively. Thus, mechanisms controlling brain tryptophan levels, i.e. the concentration of free tryptophan in serum and the intrinsic activity of the tryptophan carrier in neuronal membranes, exert in fact a tonic regulation of 5-HT synthesis in central serotoninergic neurons. 3. Changes in the rate of 5-HT synthesis can also involve modifications in the intrinsic activity of tryptophan hydroxylase. This occurs in vivo following the intrastriatal injection of kainic acid and in vitro during the depolarization of brain slices. In both cases, an activation of tryptophan hydroxylase due to an increase in its apparent Vmax is detected in soluble extracts. 4. The depolarization-induced activation of tryptophan hydroxylase in brain slices very likely involves a Ca2+-dependent phosphorylation process. 5. Rapid changes in tryptophan hydroxylase activity produced by a phosphorylation-dephosphorylation process may be involved in the phasic regulation of 5-HT synthesis in serotoninergic neurons.

Animals↗
PubMed1981

Control of 5-HT release in the caudate nucleus and the substantia nigra of the cat.

The release of 3H-5-HT newly synthesized from 3H-tryptophan was measured in the caudate nucleus (CN), the substantia nigra (SN) and the dorsal raphe nucleus (DR) of cats slightly anaesthetized with halothane. It was observed that: 1. 3H-5-HT release was 2.5 and 3.2 times higher in the DR than in the SN and the CN respectively; 2. Cooling (0 degrees C) of the DR by the use of a cryoelectrode resulted in a decrease in 3H-5-HT release in both the CN and SN; 3. Application of 5-HT (10(-7) M) into the DR induced a local increase in 3H-5-HT release, while decreasing 3H-5-HT release in the CN and SN; 4. Conversely, the blockade of 5-HT receptors in the DR by metergoline (10(-6) M) decreased the local release of 3H-5-HT and increased 3H-5-HT release in the CN. No effect was observed in the SN. These results suggest that 5-HT releases into the DR may control the activity of serotoninergic neurons.

Animals↗
PubMed1981

[Effects of intraventricular injection of 5,7-dihydroxytryptamine on monoamines and sleep in the kitten (author's transl)].

Intraventricular injections of 5,7-DHT (.15 mg/g of brain weight) were performed in kittens aged 5 or 30 days. The neurotoxin induced a significant decrease of 5-HT and NA levels in the forebrain in both age groups, whereas a slight increase of each amine was observed respectively in the raphe and lateral brain stem of the younger group (Fig. 1). Pretreatment with desmethylimipramine (20 mg/kg I.P.) resulted in a protection of the noradrenergic system from the neurotoxin (Fig. 2). From the neurophysiological standpoint, 5,7-DHT induced a major paradoxical sleep (PS) insomnia in the one-month-old group, whereas no alteration of PS was observed in the younger group (Fig. 3). The DMI pre-treatment did not modify these results. The hypothesis of brain stem sprouting is discussed, and it is concluded that the serotoninergic system does not mediate the sleep regulation in the early post-natal period.

5,7-Dihydroxytryptamine↗
PubMed1980

Effects of intraventricular injection of 6-hydroxydopamine in the developing kitten. III. Histochemical fluorescence and radioautographic studies of the noradrenaline hyperinnervation in the pons.

In the present study, using neonatal intraventricular injections of 6-hydroxydopamine (6-OHDA) and the fluorescence histochemical method for monoamines, it is observed that an extensive plexus of noradrenaline (NA) fibres develops in the pontine region of the cat brain subsequently to the neonatal destruction of the ascending NA bundles and of the NA innervation in the cerebral cortex by the neurotoxin. This plexus is only partly conserved 10 months after the 6-OHDA treatment. Generally, only a limited number of NA perikarya degenerate in the region of the locus coeruleus, the others (nucleus subcoeruleus senso lato) exhibiting the same strong fluorescence as the new NA fibres. Using the radioautographic method after intraventricular injections of [3H]NA, our work demonstrates also the transient disappearance (at least one month) of the uptake of [3H]NA in the pons, whose NA cell bodies and nerve terminals are no longer labeled in the same number as in control animals. The possibility of again labeling significantly NA perikarya and numerous nerve terminals occurred between 3 and 5 months of age, probably indicating both a re-establishment of normal uptake properties in the preserved NA perikarya and nerve terminals and some maturation of the uptake mechanisms in the abnormal NA fibres of the pons. This last observation is at variance with data from newborn animals showing that the uptake of NA develops in parallel with the accumulation of endogenous NA in catecholamine nerve terminals. The present results, however, do corroborate and complement previous biochemical data obtained in the cat after neonatal injection of 6-OHDA.

Aging↗
PubMed1980

Electrical stimulation of the nucleus raphe magnus in the rat. Effects on 5-HT metabolism in the spinal cord.

The direct electrical stimulation (with biphasic pulses of 1 msec, 10 pulses/sec, 200 microA, for 30 min) of the nucleus raphe magnus in chloral hydrate anaesthesized rats produced a significant acceleration (+50%) of 5-HT synthesis in the spinal cord as revealed by the increased rate of 5-HTP accumulation occurring at this level after the blockade of central 5-HTP decarboxylase with benserazid. In contrast, no change was detected in 5-HT metabolism in the forebrain of stimulated rats. The acceleration of 5-HT synthesis was likely not due to an increased availability of tryptophan for the rate-limiting enzyme, tryptophan hydroxylase, since the concentration of this amino acid was changed neither in the spinal cord, nor in the forebrain of stimulated rats. The measurement of tryptophan hydroxylase activity in soluble extracts from the spinal cord of control and stimulated rats revealed that the acceleration in 5-HT synthesis produced by the electrical stimulation of the nucleus raphe magnus was not associated with a persisting activation of this enzyme. Although one cannot completely exclude that a short-lasting activation of tryptophan hydroxylase, no longer detectable in soluble extracts, has occurred in the spinal cord of stimulated rats, the present findings rather suggest that the rate of 5-HT synthesis can be controlled by factors other than only the concentration of tryptophan and the intrinsic activity of tryptophan hydroxylase in serotoninergic neurons. The demonstration of an acceleration of 5-HT synthesis in bulbospinal serotoninergic neurons under stimulating conditions close to those producing analgesia in rats further supports the role of these neuronal systems in the physiological mechanisms of pain control.

5-Hydroxytryptophan↗
PubMed1980

Dopamine released from dendrites in the substantia nigra controls the nigral and striatal release of serotonin.

Using push--pull cannulae, the release of endogenously synthesized [3H]serotonin was estimated in both substantia nigra and caudate nuclei of 'encéphale isolé' cats. The unilateral nigral application of dopamine (10(-7) M) reduced [3H]serotonin release in ipsilateral structures whereas alpha-methylparatyrosine (10(-4) M) induced opposite effects. Both treatments decreased [3H]serotonin release in the contralateral caudate nucleus but not in the contralateral substantia nigra. As a working hypothesis it is suggested that the effects observed are related to changes in the activity of nigroraphe neurons regulated by dopamine release from dendrites of the nigrostriatal dopaminergic neurons. However it cannot yet be excluded that the local changes in [3H]serotonin release induced by the nigral application of dopamine or alpha-methylparatyrosine result from presynaptic modulation.

Animals↗
PubMed1979

Effect of nerve activity on the in vivo release of [3H]serotonin continuously formed from L-[3H]tryptophan in the caudate nucleus of the cat.

A new isotopic approach has been developed to study the in vivo release of serotonin (5-HT). 'Encéphale isolé' cats were implanted with a push-pull cannula in the ventrocaudal part of the head of the caudate nucleus to estimate the release of [3H]5-HT continuously synthesized from L-[3H]tryptophan. Both [3H]5-HT and [3H]tryptamine were found in superfusates. Resting steady state in the release of [3H]indoleamines was observed as soon as 20 min after the beginning of the superfusion with L-[3H]tryptophan; the levels of [3H]5-HT in superfusates were 2.5 times those of [3H]tryptamine and about 6 times the blank value. They were markedly enhanced in the presence of fluoxetine (5 x 10(-6)M), a blocker of the 5-HT uptake process. A marked increase in the release of [3H]5-HT was seen during the local depolarization of 5-HT terminals with potassium chloride (60 mM) or batrachotoxin (10(-6)M) or during the stimulation of 5-HT cell bodies in the nucleus raphe dorsalis with L-glutamic acid (5 x 10(-5)M). These treatments did not enhance the efflux of [3H]tryptamine. The potassium-evoked release of [3H]5-HT was reduced by LSD (10(-5)M). LSD added alone in the superfusing fluid was without effect. The batrachotoxin-evoked release of [3H]5-HT was inhibited in the presence of tetrodotoxin (9 x 10(-6)M). The spontaneous release of [3H]5-HT and [3H]tryptamine was markedly reduced in the presence of a calcium-free medium containing cobalt (10 mM). A transient slight reduction in the spontaneous release of [3H]5-HT was observed in the presence of tetrodotoxin (9 x 10(-6)M). The local cooling of 5-HT cell bodies with a cryoelectrode induced a slight reversible decrease in [3H]5-HT release. These last two treatments were without significant effect on [3H]tryptamine efflux in superfusates. These results indicate that the release of [3H]5-HT endogenously formed from [3H]tryptophan is dependent on nerve activity and that this is not the case for [3H]tryptamine. The advantages of the isotopic approach for in vivo studies on the release of 5-HT are discussed.

Animals↗