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Dominique Aunis

Publications and source records attributed to Dominique Aunis.

48 records · Page 3Linked to original sources
PubMed2002

The anesthetics propofol and ketamine inhibit cocaine-induced egr-1 gene expression in rat forebrain.

Acute cocaine injection to rats is known to induce the expression of immediate early genes in the forebrain, the effect being primarily mediated by the dopaminergic system. We examined the effect of the anesthetics ketamine and propofol on cocaine-induced egr-1 mRNA expression. Using in situ hybridization, we show that both compounds did not induce egr-1 gene by themselves, but were able to dose-dependently reduce cocaine-induced egr-1 mRNA synthesis in the nucleus accumbens, caudate-putamen and cingulate cortex. Our data suggest that in addition to glutamate NMDA receptors, propofol may act via GABA(A) receptors or ion channels.

Anesthetics, Dissociative↗
PubMed2002

Gamma-hydroxybutyrate increases tryptophan availability and potentiates serotonin turnover in rat brain.

Gamma-hydroxybutyrate (GHB) is both a therapeutic agent and a recreative drug. It has sedative, anxiolytic and euphoric effects. These effects are believed to be due to GHB-induced potentiation of cerebral GABAergic and dopaminergic activities, but the serotonergic system might also be involved. In this study, we examine the effects of pharmacological doses of GHB on the serotonergic activity in rat brain. Administration of 4.0 mmol/kg i.p. GHB to rats induces an accumulation of tryptophan and 5-HIAA (5-hydroxyindole acetic acid) in the frontal cortex, striatum and hippocampus without causing significant change in the tissue serotonin content. In the extracellular space, GHB induced a slight decrease in serotonin release. The tryptophan and 5-HIAA accumulation induced by GHB is mimicked by the GHB receptor agonist para-chlorophenyl-transhydroxycrotonate (NCS-356) and blocked by NCS-382 (6,7,8,9-tetrahydro-5-[H]-benzocycloheptene-5-ol-4-ylidene acetic acid) a selective GHB receptor antagonist. GHB induces the accumulation of either a derivative of or [3H]-tryptophan itself in the extracellular space, possibly by increasing tryptophan transport across the blood-brain barrier. The blood content of certain neutral amino-acids, including tryptophan, is also increased by peripheral GHB administration. Some of the effect of GHB could be reproduced by baclofen and reduced by the GABAB antagonist CGP 35348. Taken together, these results indicate that the GHB-induced stimulation of tissue serotonin turnover may be due to an increase in tryptophan transport to the brain and in its uptake by serotonergic cells. As the serotonergic system may be involved in the regulation of sleep, mood and anxiety, the stimulation of this system by high doses of GHB may be involved in certain neuropharmacological events induced by GHB administration.

Animals↗
PubMed2002

Evidence for a gamma-hydroxybutyrate (GHB) uptake by rat brain synaptic vesicles.

gamma-Hydroxybutyrate (GHB) is an endogenous metabolite of mammalian brain which is derived from GABA. Much evidence favours its role as an endogenous neuromodulator, synthesized, stored and released at particular synapses expressing specific receptors. One key step for GHB involvement in neurotransmission is its uptake by a specific population of synaptic vesicles. We demonstrate that this specific uptake exists in a crude synaptic vesicle pool obtained from rat brain. The kinetic parameters and the pharmacology of this transport are in favour of an active vesicular uptake system for GHB via the vesicular inhibitory amino acid transporter. This result supports the idea that GABA and GHB accumulate together and are coliberated in some GABAergic synapses of the rat brain, where GHB acts as a modulatory factor for the activity of these synapses following stimulation of specific receptors.

Amino Acid Transport Systems↗
PubMed2002

In vivo dopamine measurements in the nucleus accumbens after nonanesthetic and anesthetic doses of propofol in rats.

UNLABELLED: There is growing evidence that propofol acts on affective and reward processes. We designed this study to assess the effect of propofol on the concentration of dopamine in the nucleus accumbens, a main component of the mesolimbic system. The concentration of dopamine in the nucleus accumbens was assessed by using in vivo brain microdialysis in freely moving rats. A microdialysis probe was placed within guide cannulae previously placed during stereotaxic surgery. Fluid was perfused through the probe, and samples were collected every 20 min for measuring concentrations by high-pressure liquid chromatography. All rats served as their own controls and were randomized to four different doses of propofol, injected intraperitoneally: 0, 9, 60, or 100 mg/kg, according to a within design. Compared with the baseline value, dopamine concentration was decreased at the smallest dose of 9 mg/kg, whereas concentration was largely increased at the subanesthetic (60 mg/kg) and anesthetic (100 mg/kg) doses. This increase was of the same magnitude (+90%) for subanesthetic and anesthetic doses but was more prolonged at the anesthetic dose. Data show that only subanesthetic and anesthetic doses of propofol increase the concentration of dopamine in the nucleus accumbens, as previously described with drugs of potential abuse. IMPLICATIONS: Depending on the dose, propofol either increased or decreased the concentration of dopamine in the nucleus accumbens, as assessed during microdialysis in freely moving rats. Only large doses which display a pharmacological profile, such as propofol, may show promise.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2002

The nitric oxide releasing agent sodium nitroprusside modulates cocaine-induced immediate early gene expression in rat brain.

The nitric oxide (NO)/cGMP pathway triggers key events in synaptic phenomena involved in learning and memory. Using in situ hybridization, the present report demonstrates that NO released by sodium nitroprusside regulates egr-1, c-fos, and junB immediate early gene expression in rat forebrain. These genes, which are rapidly and transiently induced in response to diverse extracellular stimulation, coordinate alterations in gene expression underlying neuronal plasticity. Intracerebroventricular injection of sodium nitroprusside induced immediate early gene expression, which was highest in the nucleus accumbens. On the other hand, sodium nitroprusside abolished the cocaine-induced early gene expression in the dopaminergic projection fields nucleus accumbens, caudate-putamen, and frontal cortex. Further studies are warranted to explore the potential of the NO/cGMP/cGMP-dependent protein kinase pathway to modify cocaine-related behavioral effects.

Animals↗
PubMed2002

Mss4 gene is up-regulated in rat brain after chronic treatment with antidepressant and down-regulated when rats are anhedonic.

Differential display reverse transcription-polymerase chain reaction was used to identify mRNAs that are differentially expressed in the brain of rats treated chronically with the reference tricyclic antidepressant, imipramine, in comparison with control rats. The gene encoding for a mutation suppressor for Sec4-8 yeast (Mss4) transcript is overexpressed in the amygdala of treated rats after 3 weeks of daily administration. This overexpression is also found in the hippocampus of rats treated chronically with either tianeptine or fluoxetine. Mss4 protein has the properties of a guanine nucleotide exchange factor, interacting with several members of the Rab family implicated in Ca(2+)-dependent exocytosis of neurotransmitters. Mss4 was also overexpressed in other brain structures as judged by in situ hybridization. The kinetics of the up-regulation of Mss4 gene expression measured by Northern blot during the imipramine, tianeptine, or fluoxetine treatments are consistent with an antidepressant effect that occurs after 3 weeks. In rats in which anhedonia was induced by chronic mild stress during 3 weeks, Mss4 transcripts were specifically down-regulated in hippocampus and amygdala compared with control rats. It is proposed that Mss4 protein, which stimulates exocytosis in vivo, participates in the potentiation of the activity of neurotransmitter pathways implicated in the action of several antidepressants and constitutes one of the common functional molecules induced after chronic antidepressant treatment.

Animals↗
PubMed2002

Differential rat brain expression of EGR proteins and of the transcriptional corepressor NAB in response to acute or chronic cocaine administration.

Members of the Egr family of early genes are known to play a prominent role in neuronal plasticity. Using in situ hybridization, we report the induction in the rat forebrain of the immediate early gene egr-1 and of the transcriptional repressor NAB2 in response to acute or repeated cocaine administration. A single exposure to cocaine enhanced the expression of egr-1 in dopaminergic brain areas. Chronic cocaine treatment was not followed by induction of egr-1 mRNA initially, but only 12 h following the last injection, whereas Egr-1 binding activity was maintained elevated at 2 h and was increased again at 12 h. Expression of the Egr corepressor NAB2, but not NAB1, was rapidly and transiently stimulated by cocaine. Both acute and chronic cocaine treatment displayed biphasic NAB2 mRNA expression. It appears that NAB2 operates as an inducible regulator of gene expression in postmitotic neurons. Egr-3 displayed an expression profile similar to that of Egr-1 in response to acute cocaine injection and was expressed slightly earlier upon repeated cocaine treatment. Regulation of Egr transcription factors during chronic cocaine treatment appears to differ from that of the AP1 transcription factor, since Egr-1 and Egr-3 were induced after both acute and repeated cocaine administration, and that neither Egr-2 nor Egr-3 substituted for Egr-1 after chronic cocaine treatment. Our data suggest that Egr-1, Egr-3, and NAB2 are the key members of their families that regulate expression of Egr target genes.

Animals↗
PubMed1995

Immunohistochemical Localization of Chromostatin and Pancreastatin, Chromogranin A-Derived Bioactive Peptides, in Normal and Neoplastic Neuroendocrine Tissues.

Despite the widespread distribution of chromogranin A (CgA) in neuroendocrine tissues, the biological function of CgA has not yet been elucidated. The primary amino acid sequence of CgA, elucidated by cDNA analysis, has been revealed to include several pairs of basic amino acid residues that are homologous to the bioactive peptides, such as pancreastatin (PST) and chromostatin (CST). Using antibodies for human PST and CST, the immunohistochemical localization of these peptides was investigated in neuroendocrine tissues, including human pituitary glands, pancreas, adrenal medulla, various types of neuroendocrine neoplasms (13 pheochromocytomas, 10 medullary thyroid carcinomas, 11 pancreatic endocrine tumors, and 19 carcinoid tumors), and the cell line QGP-1N derived from human somatostatin-producing pancreatic endocrine tumor. Variable immunoreactive intensities of PST and CST were seen, but both peptides were detectable in all neuroendocrine tissues and in most of the neoplasms. Immunoreactivity for both PST and CST was observed in 100 and 73%, respectively, of pancreatic endocrine tumors, all pheochromocytomas, and 80 and 40%, respectively, of medullary thyroid carcinomas, as well as all nonrectal carcinoid tumors. In rectal carcinoids, cells immunoreactive for PST and CST were sparse. The distribution of PST and CST was similar to that of CgA, and it is considered that these peptides are simultaneously processed from CgA, and may play roles in autocrine and paracrine regulation on various hormones in addition to their previously known functions.

Journal Article↗
PubMed1992

Two GTP-binding Proteins Control Calcium-dependent Exocytosis in Chromaffin Cells.

The effect of guanosine triphosphate analogues on catecholamine secretion from permeabilized bovine chromaffin cells was examined. Guanosine 5'-[gamma-thio]triphosphate was demonstrated to produce a dual effect on calcium-evoked secretion, enhancing the release through a mechanism involving protein kinase C and inhibiting secretion by a protein kinase C-independent pathway. We propose that two functionally distinct G-proteins control the stimulus - secretion coupling in chromaffin cells.

Journal Article↗
PubMed1992

Noradrenergic, but not Adrenergic Chromaffin Cells in the Adrenal Gland Express Neuromodulin (GAP-43).

Neuroendocrine chromaffin cells of the adrenal gland express certain molecular markers either transiently during development or permanently. In the present study, the expression of neuromodulin (GAP-43), a neuronal protein often associated with neurite outgrowth, was examined in adult adrenals. Neuromodulin was detected by Western blot analysis in extracts of both rat adrenals and cultured bovine chromaffin cells, and was localized in situ in a subpopulation of chromaffin cells, as well as in nerve fibres and Schwann cells. The use of anti-tyrosine hydroxylase or anti-phenylethanolamine N-methyltransferase antibodies in combination with anti-neuromodulin antibodies in double immunofluorescent labelling of cryostat sections of rat glands demonstrated that neuromodulin is expressed by noradrenergic, and not by adrenergic chromaffin cells. The results provide further evidence that neuromodulin is not limited to neurons; it is also expressed in a subpopulation of neuroendocrine chromaffin cells. Neuromodulin may play a role in the development of the adrenal medulla or in the specific regulation of noradrenalin secretion from chromaffin cells.

Journal Article↗
PubMed1992

L1 Cell Adhesion Molecule is Expressed by Noradrenergic but not Adrenergic Chromaffin Cells: A Possible Major Role for L1 in Adrenal Medullary Design.

The adrenal medulla of higher animals is constituted of homotypic groups of chromaffin cells secreting either adrenalin or noradrenalin. Since not all chromaffin cells are individually innervated by fibres of the splanchnic nerve, this tissue characteristic is crucial to the physiological function of the gland. In an attempt to analyse differences between these chromaffin cell types which might underlie the establishment of this tissue pattern, we examined the expression of the adhesion molecule L1 in this gland by immunocytochemistry at the optical and ultrastructural levels in rats. L1, an adhesion molecule abundant in the central nervous system, was found to be present in the adrenal medulla of adults; it was strongly expressed on innervating axons and their surrounding Schwann cells and also on a subpopulation of chromaffin cells. The nature of these chromaffin cells was examined by immunocytochemistry using antibodies against the catecholamine-synthesizing enzyme phenylethanolamine N-methyltransferase (PNMT), which are capable of distinguishing between adrenergic and noradrenergic cells. Immunofluorescence labelling of sequential frozen sections demonstrated that chromaffin cells which express L1 do not express PNMT; conversely, L1 was not detected in any chromaffin cells expressing PNMT. Ultrastructural immunocytochemistry confirmed the existence of two non-overlapping populations of chromaffin cells. It is concluded that, in the adrenal medulla, noradrenergic but not adrenergic chromaffin cells express this adhesion molecule. These data, together with our previous observations that all chromaffin cells express the neural cell adhesion molecule, NCAM, suggest that L1, in cooperation with NCAM, could be responsible for the association of noradrenergic cells in the form of homotypic aggregates segregated from groups of adrenergic cells within the adrenal medulla.

Journal Article↗