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J F Pujol

Publications and source records attributed to J F Pujol.

At least 19 recordsLinked to original sources

Correlation between the increase in tyrosine hydroxylase activity and the decrease in serotonin content in the rat locus coeruleus after 5,6-dihydroxytryptamine.

A correlation is demonstrated between the increase in tyrosine hydroxylase activity and the decrease in serotonin concentration in the rat locus coeruleus after various doses of 5,6-dihydroxytryptamine and gradual protection of serotonin neurons by pretreatment with two serotonin uptake inhibitors: fluoxetine or citalopram.

5,6-Dihydroxytryptamine

GABA-accumulating neurons in the nucleus raphe dorsalis and periaqueductal gray in the rat: a biochemical and radioautographic study.

The possibility of a GABAergic innervation of the nucleus raphe dorsalis (NRD) has been investigated by using the following approaches: (i) the identification of the principal neuronal groups afferent to the NDR by using horseradish peroxidase retrograde transport, (ii) the determination of glutamate decarboxylase activity (GAD) in the NRD after lesioning these groups or their putative pathways, and (iii) the radioautographic identification of terminals axons and nerve cells accumulating intraventricularly injected [3H]GABA. The hypothesis of a local GABAergic network is supported by the failure to obtain important changes in GAD after lesions of NRD afferents and the presence in this nucleus of terminals, fibers and nerve cell bodies accumulating [3H]GABA. It appears that these GABA-accumulating neurons could represent a portion of aperiventricular GABAergic system in the periaqueductal gray and the pontine ventricular gray.

Afferent Pathways

The efferent connections of the nucleus raphe centralis superior in the rat as revealed by radioautography.

By chronically implanting a glass micropipette filled with tritiated leucine in the raphe centralis superior of the rat, the projection of this nucleus was traced by radioautography. The majority of the ascending projections were located within the ventral tegmental area and, further rostrally, the median forebrain bundle. Along the course of this bundle numerous fibers branched successively into the mammillary peduncle, the fasciculus retroflexus, the stria medullaris, the fornix and the cingulum. The most significant projections included the ones to the interpeduncular nucleus, the mammillary bodies, the habenular nuclei and the hippocampus. No projections were detected in the striatum, the cortex piriformis or the amygdala. Descending projections diffused to the pontine reticular formation and central gray through the medial and the dorsal longitudinal bundles. In addition widespread projections were also seen in nuclei located near the raphe centralis superior: raphe nuclei, dorsal and ventral tegmental nuclei.

Animals

Distribution of adrenaline-synthesizing enzyme activity in the human brain.

A study of the distribution of phenylethanolamine-N-methyl-transferase (PNMT) activity in normal human brain is presented. After a preliminary dissection to separate brain tissue for formalin fixation and tissue designed for biochemical studies, the hemi-brain stem is cut in slices by hand and a cerebral hemisphere is cut on a cyromicrotome. "Punches" are made with an operating microscope. The dissection method was used to study the distribution of PNMT activity in 117 "punches" made on 21 slices obtained from 5 normal human brains. The caudo-rostral distribution of PNMT activity in C1 and C2 groups was found to be identical in each brain. The distribution of PNMT activity was found to be similar to that in the rat, but, in addition, important activity was found in the substantia nigra, internal pallidium and nucleus accumbens.

Brain

High resolution radioautographic identification of [3H]GABA labeled neurons in the rat nucleus raphe dorsalis.

Following intraventricular administration of [3H]GABA into the lateral ventricle of the rat radioautography demonstrates the presence of labeled cell bodies and fibers within the nucleus raphe dorsalis (NRD). Pharmacological controls suggest that labeled perikarya whose diameter does not exceed 10 micrometer and which are not probably more than ten in the entire NRD could be GABAergic. The effects of 5,7-dihydroxytryptamine (5,7-DHT) pretreatment support the hypothesis that labeled fibers could belong at least to two populations: ones being probably serotonergic and the others being possibly GABAergic. These results are in good agreement with the existence of an intrinsic GABAergic system within the rat NRD.

Animals

Participation of serotonin in thyrotropin release. II. Evidence for the action of serotonin on the phasic release of thyrotropin.

During a 12-h light 12-h dark schedule (lights off at 1900 h), male Sprague-Dawley rats show a circadian rhythm of plasma TSH with a zenith near midday. The participation of serotonin (5HT) in the phasic release of TSH was studied using both pharmacological and surgical-stereotaxical approaches. Animals treated with parachlorophenylalanine methyl ester (pCPA), an inhibitor of 5HT synthesis (one or two injections of 250 mg/kg each) showed a reduction or a disappearance of the diurnal peak of TSH, respectively. Additional treatment by 5-hydroxytryptophan, a precursor of 5HT, completely, restored the diurnal TSH peak. Treatment with 5,6-dihydroxytryptamine creatine sulfate, a neurotoxin which selectively destroys 5HT terminals, also induced alterations of the diurnal peak of TSH. There were no major modifications observed in the low nocturnal levels of TSH in rats treated with pCPA, 5-hydroxytryptophan, or 5,6-dihydroxytryptamine. The major serotoninergic innervation of the hypothalamus originates from the raphe dorsalis or centralis; destruction of these two nuclei caused a quasiabolition of the diurnal TSH peak (only a low amplitude TSH circadian rhythm persisted). Hypothalamic 5HT content was measured in the majority of these experiments; the greatest depletions (near 90%) were observed after two injections of pCPA or in rats bearing raphe lesions. We conclude that the diurnal peak of TSH, observed during the physiological circadian rhythm, is serotoninergic dependent.

5,6-Dihydroxytryptamine

Early increase in phenylethanolamine-N-methyltransferase activity in a new strain of spontaneously hypertensive rats.

By repeated inbreeding, 2 strains of spontaneously hypertensive and normotensive rats have been simultaneously selected. The activities of tyrosine hydroxylase and phenylethanolamine-N-methyltransferase were determined in various central catecholaminergic nuclei (C1, C2, A6 and A9) and in two peripheral tissues (adrenal glands and superior cervical ganglion). These assays were performed on rats belonging to the normotensive or the hypertensive strain at 3 ages which characterize the development of hypertension (5, 9 and 21 weeks). Except for a decrease in the C1 region of 9-week-old rats, no significant change in tyrosine hydroxylase activity occurred in central or peripheral structures of the spontaneously hypertensive rats when compared to the normotensive rats. In contrast, the activity of the phenylethanolamine-N-methyltransferase (PNMT), was increased in the C2 adrenergic group of the medulla oblongata in young spontaneously hypertensive rats: +43% (P less than 0.001) at 5 weeks of age and +32% (P less than 0.001) in 9-week-old rats. However, there was no significant difference between the 21-week-old rats. No modification of the PNMT activity was found in the C1 adrenergic group of the medulla oblongata. PNMT activity was increased significantly in the adrenal glands of 5-week-old hypertensive rats (+22%, P less than 0.001). By 9 weeks, the difference in PNMT activity in the adrenals was no longer significant. Thus, in young rats of the hypertensive strain, there was an increase in the capacity to synthetize adrenaline in the C2 area of the medulla oblongata and in the adrenal glands. While the enzymatic change present in the adrenals seems to be specific to this new strain of hypertensive rats, the elevation of PNMT activity in a specific region of the medulla oblongata (C2 group) is a characteristic common to at least two independently derived strains of genetically hypertensive rats.

Adrenal Glands

[Identification of GABA accumulating neurons in the dorsal raphe nucleus].

A possible GABAergic innervation of the nucleus raphe dorsalis (NRD) was investigated by measuring glutamate decarboxylase activity in the NRD after lesioning the afferents of this nucleus. The slight decrease found in the enzymatic activity suggests that these afferents have a minor participation in the GABA innervation of the NRD and implies the existence of an intrinsic GABAergic system in this nucleus. This local innervation was demonstrated by radio-autography and shows fibers, axonal varicosities and cell bodies which accumulate 3H GABA in the caudal part of this nucleus.

Animals

[In vivo continuous electrochemical determination of dopamine release in rat neostriatum].

Polarographic micro-electrodes (carbon fiber, o. d. 8 micron) implanted in the Rat caudate nucleus, allowed a practically continuous in vivo monitoring (one measurement every 5 sec.) of the extra-cellular concentration of dopamine released by striatal dopaminergic terminals. Administration of amphetamine produced a reproducible increase of the oxidation current. This effect was suppressed after the selective degeneration of the striatal dopaminergic terminals following the injection of 6-OHDA into the substantia nigra or after inhibition of the synthesis of the amine by alpha methyl-p-tyrosin. After 5 hrs. this drug produced a 70% decrease of the oxidation current.

Animals

Increase of ornithine decarboxylase activity elicited by reserpine in the peripheral and central monoaminergic systems of the rat.

Ornithine decarboxylase activity was increased about tenfold in adrenal glands and in brain regions preponderantly containing aminergic neurons, by a single dose of 16 mumol/kg of reserpine. Maximal enzyme activity in the adrenal glands was observed at about 8 hr after reserpine administration. The ornithine decarboxylase activity-time curves in the brain regions showed a concomitant polyphasic course, with the highest maximum at 12 hr postinjection. Ornithine decarboxylase induction is discussed as an early event in the cascade of molecular events preceding the induction of cell typic enzymes.

Adrenal Glands

Daily variations of various parameters of serotonin metabolism in the rat brain. I. Circadian variations of tryptophan-5-hydroxylase in the raphe nuclei and the striatum.

Daily changes in tryptophan-5-hydroxylase (TrH) activity have been studied in six different 5-HT-containing cell groups (B3, B4, B5, B6, B7, B8,) in the brain stem of rats maintained in a regular cycle of 12 h of light and 12 h of darkness. Significant circadian alternations of TrH activity were observed in most of the raphe nuclei tested, although the changes were not identical from one structure to another. The striatum showed daily variations in TrH activity in opposite phase to the nucleus raphe dorsalis which projects specific terminals into this area. Monoamine oxidase (MAO) activity was simultaneously estimated in these nuclei but did not exhibit and significant rhythm, suggesting a specific regulation of TrH. Total protein levels were also subject to daily changes.

Animals

Daily variations of various parameters of serotonin metabolism in the rat brain. II. Circadian variations in serum and cerebral tryptophan levels: lack of correlation with 5-HT turnover.

Rats submitted to regular 12 h cycles of light and darkness for three weeks were sacrificed at various times of the day. 5-HT, 5-HIAA and tryptophan levels were estimated in the fronto-parietal cerebral cortex. Tyrosine and free and total tryptophan levels in serum were estimated in parallel. Significant circadian variations in 5-HT and 5-HIAA levels were found in cerebral tissues. The peaks of 5-HIAA levels were dectected during the lignt and dark periods respectively, the maximal fluctuations being seen between 17.00 h and 21.00 h, two times separating the light off. Important significant circadian variations in free and total serum tryptophan levels were also observed. In both cases, the maximal levels were found during the middle of the dark phase after the peak of 5-HIAA levels. The circadian rhythm of tyrosine levels in serum was in opposite phase with that of tryptophan (free or total). The diurnal changes in tryptophan content in cerebral tissues seemed thus related to those found in serum. Taking in consideration results obtained in previous studies 16,17 carried out in similar experimental conditions, it was concluded that the parallel increase in serum free tryptophan and in tissues 5-HIAA levels seen during the night were not related to a stimulation of 5-HT turnover. Indeed 5-HT synthesis is minimal at this time16.

Amino Acids