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Biomedical subjects

M Hamon

Publications and source records attributed to M Hamon.

At least 487 records · Page 27Linked to original sources
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

[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↗
PubMed1981

Serotoninergic control of punished behavior: effects of intra-raphe microinjections of chlordiazepoxide, GABA and 5-HT on behavioral suppression in rats.

The effects of intra dorsalis raphe microinjections of chlordiazepoxide, GABA and 5-HT were studied on a model of behavioral suppression in rats. The suppression of responding for food was elicited by a 10 min presentation of a signal previously associated with the delivery of electric foot shocks. Microinjections of chlordiazepoxide, GABA and 5-HT (0.2 microliters) performed in awake hand-held rats reduced the behavioral suppression. Chlordiazepoxide and 5-HT acted in a synergistic way, while such a synergy could not be obtained when chlordiazepoxide and GABA were coadministered. Moreover, the effects of intra-raphe chloridazepoxide no longer appeared in rats given intra dorsalis raphe 5-7 dihydroxytryptamine (3 micrograms in 0.4 microliters) 3 weeks before testing. All these results further support the hypothesis of the involvement of 5-HT neurons both in punishment-induced inhibition and in the antipunishment activity of benzodiazepines. No evidence was obtained suggesting a GABAergic mediation for the functional interaction of chlordiazepoxide with 5-HT neurons in this experimental model. Since high 3H-flunitrazepam binding was found at the raphe dorsalis level, and since a 30% decrease in the number of intra-raphe 3H-flunitrazepam binding sites was detected after intra-raphe 5-7 dihydroxytryptamine, it is possible that intra-raphe chlordiazepoxide controls 5-HT neurons partly through some benzodiazepine binding sites located on 5-HT cells.

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

Decreased convulsant potency of picrotoxin and pentetrazol and enhanced [3H]flunitrazepam cortical binding following stressful manipulations in rats.

Various stressful manipulations in rats (cold-water swim, electric foot-shock administration, imparied access to food reward) were found to reduce the convulsant potency of drugs which interfere with GABA or benzodiazepine central processes. The convulsant threshold dosages of picrotoxin (0.4 mg/ml) or pentetrazol (10 mg/ml) administered after the stress by infusion (0.2 ml/min) via a vein of the tail were enhanced. The onset of generalized seizures induced by isoniazid (800 mg/kg) or by thiosemicarbazide (64 mg/kg) i.p. was delayed after cold-water swim. However, convulsant threshold dosages of bemegride or strychnine perfused at 2 and 0.2 mg/ml respectively were not changed by stress. Cold-water swim increased the number of cortical (but not cerebellar) [3H]flunitrazepam binding sites (+ 24%) but failed to alter cortical [3H]muscimol binding. This post-stress enhancement of binding sties, although suppressed by bicuculline (10(-4) M) seems not to be dependent on GABAergic mechanisms. Indeed cold-water stress did not reduce the ability of muscimol (10(-6) and 10(-5) M) and GABA (5 x 10(-6) and 5 x 10(-5) M) to increase flunitrazepam binding. Finally, this post-stress enhancement of benzodiazepine binding was not found to be paralleled by changes in the protective effects of diazepam against picrotoxin- or pentetrazol-induced seizures.

Animals↗
PubMed1980

Characteristics of serotonin receptors in the rat brain.

Two biochemical methods are currently available for studying 5-HT receptors in the central nervous system. The first consists of measuring the specific high affinity binding of 3H-5-HT to synaptic membranes. The other derives from the discovery of an adenylate cyclase which can be activated by 5-HT in brain homogenates. Whereas the specific 3H-5-HT binding is measurable in young as well as in adult rats, the 5-HT-sensitive adenylate cyclase can be quantitatively estimated only during the first three weeks following birth. Later on, the increment of adenylate cyclase activity produced by 5-HT is too low to permit valid measurements, notably in tissues from adult rats. Studies on the effects of various agonists and antagonists demonstrated that the specific binding site characterized by a high affinity for 3H-5-HT (Kd = 1.5 nM) exhibited the expected properties of a 5-HT receptor in brain. Performing chemical lesions on serotoninergic neurons by an intracerebral injection of 5, 7-dihydroxytryptamine or the blockade of central 5-HT receptors by the peripheral administration of methiothepin resulted in a subsequent increase in the number of specific binding sites for 3H-5-HT particularly in the hippocampus (+30 to +45%). In contrast, preliminary attempts to detect any supersensitivity of the 5-HT-sensitive adenylate cyclase after selective raphe lesions were unsuccessful. Indeed, several observations strongly suggested that the high affinity binding site for 3H-5-HT did not correspond to the 5-HT receptor coupled to adenylate cyclase in synaptic membranes: 1) the apparent affinity of the 5-HT-sensitive adenylate cyclase for 5-HT was about 300 times lower (Kd = 0.5 microM) than that of the specific 3H-5-HT binding site; 2)the ontogenic evolutions of 3H-5-HT binding and 5-HT-sensitive adenylate cyclase were not parallel, notably in the hippocampus; 3) they were differently affected by several drugs. For instance, quipazine, a putative 5-HT agonist, effectively displaced 3H-5-HT from its specific binding site (Ki = 0.23 microM) whereas it did not affect 5-HT-sensitive adenylate cyclase. In conclusion, it is likely that the high affinity binding site for 3H-5-HT and the 5-HT-sensitive adenylate cyclase belong to two different postsynaptic 5-HT receptors in the rat brain.

Adenylyl Cyclases↗
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↗
PubMed1979

Effects of intraventricular injection of 6-hydroxydopamine in the developing kitten. 1. On the sleepwaking cycles.

Intraventricular 6-OHDA was injected in kittens at different stages of development, and the subsequent sleep polygram was analyzed, in order to determine the role of the catecholaminergic system in the ontogenesis of sleep regulations during the first and the second postnatal months. 6-OHDA, used with or without previous chlorimipramine treatment, led within a 10-day period to drastic reductions of the endogenous monoamines in the forebrain of all age groups. Although the neurotoxicity of 6-OHDA was almost constant among the different age groups, the effects on sleep depended on the age of the animals at the time of the injection. In the 5-week-old injected kittens, 6-OHDA affected PS according to an adult-like pattern. In the 3-week-old kittens, 6-OHDA alone (leading to both catecholamines and serotonin decreases) induced the same PS deficit as in the adult cat. In the 1- and 2-week-old kittens, neither 6-OHDA alone, nor 6-OHDA with previous chlorimipramine treatment, distrubed the sleep regulations. These data are compared to similar experiments performed in the adult cat. They are discussed in terms of sleep control ontogenesis. It is concluded that the catecholaminergic system plays no important role in the mechanisms of sleep regulation in the early postnatal period in the kitten, whereas its regulatory influence on PS is confirmed in the juvenile animal. The functional maturation of the catecholaminergic system in terms of sleep regulation is achieved between the third and the fifth week of postnatal life.

Age Factors↗