Biomedical subjects

M Daoust

Publications and source records attributed to M Daoust.

12 recordsLinked to original sources

PubMed1992

Acamprosate modulates synaptosomal GABA transmission in chronically alcoholised rats.

Male Sprague-Dawley rats were pulmonary alcoholised for 30 days. Six were treated with acamprosate (400 mg/kg/day, PO) during alcoholisation. The control nonalcoholised group also received acamprosate (400 mg/kg/day, PO) during the 30 days. At the end of the experiment, brains areas (cortex, hippocampus, thalamus, striatum, and olfactory bulbs) were dissected for the study of synaptosomal 3H-GABA uptake. In another experiment, GABA levels were determined in the same areas using HPLC with electrochemical detection. Blood ethanol levels were also measured during alcoholisation. Acamprosate treatment did not modify blood ethanol levels. In cortex and olfactory bulbs, alcoholisation increased 3H-GABA uptake (Vmax) with an increase in the affinity (Km). 3H-GABA uptake was not affected by alcoholisation in other brain areas. In hippocampus and thalamus, acamprosate treatment enhanced 3H-GABA uptake (Vmax) only in alcoholised rats. Moreover, in thalamus, alcoholisation enhanced GABA levels. The effect of alcohol and acamprosate on GABA presynaptic events is discussed and it is concluded that the action of ethanol and acamprosate on GABA transport could be, in part, responsible for the modulation by acamprosate treatment of ethanol behaviour.

Acamprosate↗

PubMed1992

Triptosine, an L-5-hydroxytryptophan derivative, reduces alcohol consumption in alcohol-preferring rats.

Triptosine is a new L-5-hydroxytryptophan derivative whose effect has been studied in the Long-Evans alcohol-preferring rat. At an oral dose of 100 mg/kg once daily, triptosine reduced alcohol consumption by 42% in the second week of treatment and increased that of water by 80%. The results suggest that this precursor of serotonin might play an important role in diminishing preference for alcohol and reaccustoming the animal to water, without exerting an anorexic effect.

5-Hydroxytryptophan↗

PubMed1992

Tianeptine, a specific serotonin uptake enhancer, decreases ethanol intake in rats.

The effect on ethanol intake of the selective 5-HT uptake enhancer tianeptine was examined in rats and compared with that of fluoxetine, a specific 5-HT uptake inhibitor. Both treatments significantly decreased ethanol intake (54% by tianeptine and 57% by fluoxetine). Fluoxetine also decreased food intake whereas tianeptine did not. Body weight was decreased by 12.5% in fluoxetine-treated rats but was not modified by tianeptine. It is proposed that tianeptine has a specific action on ethanol intake, possibly related to its effect on serotonin function.

Alcohol Drinking↗

PubMed1991

Ethanol intake and 3H-serotonin uptake I: A study in Fawn-Hooded rats.

Ethanol intake and synaptosomal 3H-serotonin uptake were studied in male Fawn-Hooded and Sprague-Dawley rats. Fawn-Hooded rats consumed more alcohol and more water than Sprague-Dawley rats. Plasma alcohol levels of Sprague-Dawley rats were not detectable but were about 5 mg/dl in Fawn-Hooded rats. Ethanol intake increased the Vmax of serotonin uptake in Fawn-Hooded rats in hippocampus and cortex, but not in thalamus. In Fawn-Hooded rats, serotonin uptake (Vmax) was higher than in Sprague-Dawley rats cortex. Ethanol intake reduced the Vmax of serotonin uptake in Fawn-Hooded rats in hippocampus and cortex. In cortex, the carrier affinity for serotonin was increased in alcoholized Fawn-Hooded rats. These results indicate that synaptosomal 3H-serotonin uptake is affected by ethanol intake. In Fawn-Hooded rats, high ethanol consumption is associated with high serotonin uptake. In rats presenting high serotonin uptake, alcoholisation reduces 3H-serotonin internalisation in synaptosomes, indicating a specific sensitivity to alcohol intake of serotonin uptake system.

Analysis of Variance↗

PubMed1991

Ethanol intake and 3H-serotonin uptake. II: A study in alcoholic patients using platelets 3H-paroxetine binding.

The kinetic parameters of 3H-paroxetine binding and 3H-serotonin uptake were studied in platelets of alcoholic patients. There was no difference between alcoholic and non alcoholic subjects in 3H-paroxetine binding. When binding and 3H-serotonin uptake were studied, in the same plasma of the same subjects, the Vmax of serotonin uptake was increased in alcoholics. The data confirm the involvement of serotonin uptake system in alcohol dependence and suggest that serotonin uptake and paroxetine binding sites may be regulated independently in this pathology.

Adult↗

PubMed1991

[Benzodiazepine receptors during various treatments of alcohol withdrawal].

Drugs most commonly used in the treatment of alcoholic withdrawal are antianxiety agents, namely benzodiazepines. Some similarities may be found between the mechanism of action of such active principles and that of alcohol at the GABAergic transmission level. In mice with physical dependence, in vivo binding of [3H]-RO 15-1788 to central benzodiazepine receptors increases during the initial period, but then tends to taper down to its basal value in the course of withdrawal. Neurochemical treatment with alpha-adrenergic drugs or with agents than can stimulate serotonergic transmission, as opposed to meprobamate therapy, promotes faster recovery of basal levels. In man, these data may be referred to decreased benzodiazepine consumption in the course of alcohol withdrawal. The results suggest that both noradrenergic and serotonergic treatments may be associated with significantly lower risks for newly induced benzodiazepine dependence.

Animals↗

PubMed1991

Comparison of oral bioavailability of two dosage-forms of progesterone in women.

For poorly water soluble drugs, the dissolution process in biological fluids the rate limiting step in absorption. However, the utilization of some galenic processes such as solid dispersions (SD) leads to an improvement in quality and intensity of the drug gastro-intestinal absorption. In a previous work, the in vitro studies of the dissolution curves of both the pure micronized progesterone (MP) and the progesterone-PEG 6000 SD revealed marked increases in the progesterone dissolution rates for all the SD investigated compared to the pure MP. The aim of this work was to investigate the in vitro results after oral administration of the two pharmaceutical forms to menopaused volunteer women.

Administration, Oral↗

PubMed1990

Noradrenergic system: effect of DSP4 and FLA-57 on ethanol intake in ethanol preferring rats.

Ethanol preferring rats (male Long-Evans; n = 6) were selected as drinking rats (DR) and treated with DSP4 (50 mg.kg-1 IP) at the end of the preference selection. Two more groups received DSP4 (50 mg.kg-1 IP) + the inhibitor of dopamine beta-hydroxylase FLA-57 (1 mg.kg-1.d-1 during two weeks), IP (n = 5) or FLA-57 alone (1 mg.kg-1.d-1 during two weeks IP) (n = 5). The control DR group (n = 6) received NaCl 0.9%. 3H-Noradrenaline uptake was studied at the 17th day of treatment in DR, treated or not with DSP4, and in ethanol naive rats treated (n = 6) or not (n = 6) with DSP4 (50 mg.kg-1, IP) DSP4 does not modify ethanol intake in DR, and both treated groups (DR or ethanol naive rats). 3H-Noradrenaline uptake was decreased (about 60%), both in cortex and hippocampus. But the association of FLA-57 and DSP4 decreases both ethanol and fluid intakes. It was suggested 1) that the 40% of intact neurons was able to compensate the DSP4-induced noradrenergic neurons destruction, 2) that the destruction of noradrenergic pathways (FLA-57 + DSP4) is associated with a decrease in ethanol intake but also in fluid intakes, suggesting finally 3) that the modulation of ethanol intake by the noradrenergic system was partial or indirect.

Alcohol Drinking↗

PubMed1990

Acamprosate appears to decrease alcohol intake in weaned alcoholics.

Five hundred and sixty-nine alcoholics were included in a double-blind placebo-controlled randomized multicenter study of the effects of Acamprosate (calcium acetylhomotaurinate (CA), 1.3 g/day) on indicators of alcoholic relapse after withdrawal. One hundred and eighty-one patients in the CA group versus 175 in the placebo group completed the three-month study. The major efficacy criterion was plasma gamma-glutamyl transpeptidase (GGT), as an indicator of recent alcohol ingestion. This analysis was completed by criteria concordance analysis on a number of indicators of alcohol intake. Patients in both groups were similar initially. After 3 months of treatment, the patients in the CA group had significantly lower GGT (1.4 +/- 1.56 versus 2.0 +/- 3.19 times normal, P = 0.016). All significant differences (P less than 0.05) or trends (0.10 greater than P greater than 0.05) were in favor of a superior effect of CA over placebo. The major side-effect of CA was diarrhea (present in 13% of CA patients versus 7% of placebo, P = 0.04). CA proved superior to placebo on the evolution of markers of alcohol ingestion at three months, in this large-scale multicenter study. It could be a new modality in the drug therapy of alcoholism, not involving an antabuse effect, an antidepressant action, or conditioning.

Acamprosate↗

PubMed1990

Alcohol and GABA: ethanol intake modifies hippocampal nipecotic acid binding in ethanol-preferring and non-preferring rats.

3H-nipecotic acid (3H-NIP) binding to GABA uptake recognition sites was studied in the hippocampus of 3 groups of male, Long Evans rats: Group 1: ethanol-naive rats (ENR); Group II: ethanol-preferring rats (DR) and non-preferring rats (NDR), which had consumed about 5 g.kg-1.d-1 and 1 g-1.d-1 of alcohol respectively in the form of a 12% ethanol solution prior to 3H-NIP binding analysis; Group III: DR and NDR who had had no access to ethanol for 21 d after the initial exposure of ethanol solution (28 d). Binding studies showed that ethanol drunk by both DR and NDR in Group II decreased 3H-NIP binding (Bmax decreased) with an enhancement of affinity (KD decreased). In rats subjected to withdrawal of ethanol (Group III), affinity of 3H-NIP for GABA uptake sites was higher than in controls (Group I), but lower than in Group II, Bmax in this group being higher than in the 2 other groups. In Group III, KD was higher in DR than in NDR. These results showed that ethanol intake, in a free-choice paradigm, altered 3H-NIP binding, and that differences in ethanol intake between DR and NDR were associated with differences in sensitivity of hippocampal GABA uptake sites. These differences in 3H-NIP binding could either precede ethanol intake, or be a direct result from it. The results, together with data from other laboratories suggest that: 1), 3H-NIP binding sites are involved in the regulation of ethanol intake; 2), 1 factor responsible for individual differences in ethanol response is reflected by the GABA uptake system.

Animals↗

PubMed1986

Dynamic characteristics of dopamine, norepinephrine and serotonin metabolism in axonal endings of the rat hypothalamus and striatum during hypoxia: a study using HPLC with electrochemical detection.

The metabolism of dopamine, norepinephrine and serotonin was studied in normoxic or hypobaric hypoxic rats, using HPLC with electrochemical detection. The changes in serotonin and its metabolite 5 hydroxy indolacetic acid (5 HIAA) levels in the hypoxic striatum and hypothalamus suggest an inhibition of 5 HIAA formation and a complex interaction between synthesis, release and uptake. Hypoxia caused a decrease of the striatal levels of homovanillic acid (HVA), dihydroxy 3-4 phenylacetic acid (DOPAC) [inhibition of tyrosine hydroxylase (TH) and monoamine oxidase (MAO)] and 3-methoxytyramine (3 MT) (inhibition of release). Striatal dopamine levels were increased, suggesting an increase in granular dopamine storage, with an impaired release. Hypothalamic levels of norepinephrine were decreased during hypoxia [(inhibition of TH, MAO, and dopamine beta-hydroxylase (DBH)].

3,4-Dihydroxyphenylacetic Acid↗

PubMedDate not supplied

[Alcohol and the serotonin system].

There is considerable evidence from animal and human studies that serotonin plays a role in the modulation of alcohol intake and/or alcohol dependence. Biochemical, behavioral and pharmacological studies both in animal and man had verified this hypothesis. Central and peripheral levels of serotonin and of its metabolite 5-hydroxyindoleacetic acid (5-HIAA) are modified by alcoholisation. Moreover, the use of pharmacological drugs modifying specifically serotonin transmission decreases ethanol intake. Our own studies suggest that a dysfunctioning of serotonin uptake system could be implicated in the individual risk of alcohol dependence. Even if other systems, e.g. amino acids, are involved in the regulation of alcohol behavior, all data are in favor of a modulation of alcohol intake by serotonin transmission.

Alcohol Drinking↗