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D Lévesque

Publications and source records attributed to D Lévesque.

45 records · Page 3Linked to original sources

Striatal D1 dopamine receptor density fluctuates during the rat estrous cycle.

Striatal D1 dopamine (DA) antagonist binding sites were investigated in intact female and male rats, ovariectomized (OVX) animals and during the 4-day estrous cycle. The affinity of the striatal D1 receptor as labelled with [3H]SCH 23390 remains unchanged in intact male, female rats during the estrous cycle and OVX animals. By contrast, ovariectomy decreased striatal D1 receptor density by 17% (P less than 0.01) compared to intact female rats while a small but significant higher density was observed in intact male compared to female rats (10% higher, P less than 0.05). The density of striatal D1 DA receptor was higher on the day of diestrus I (DI) and diestrus II (DII) (P less than 0.01 vs OVX) and fluctuates throughout the estrous cycle with a maximum on the day of DII (P less than 0.05 vs proestrus PM). Our results show for the first time that striatal D1 DA receptors fluctuate during the estrous cycle and can be modulated by gonadal steroids.

Animals↗

Chronic estradiol treatment increases ovariectomized rat striatal D-1 dopamine receptors.

Striatal D-1 dopamine (DA) receptors were investigated following chronic 17 beta-estradiol (10 micrograms, b.i.d., s.c., for two weeks) to ovariectomized (OVX) female rats. This treatment initiated the day after ovariectomy has revealed that the maximal density in homogenates of striatal D-1 DA receptors (Bmax) labelled with [3H] SCH 23390 was increased (44% without and 28% with 120 mM NaCl in the assay buffer). Estradiol treatments initiated 2 or 4 weeks after ovariectomy did not induce D-1 DA receptor binding modifications. The affinity (Kd) of the ligand for the receptor remains unchanged by the steroid treatment while NaCl increased both the density and the affinity of [3H] SCH 23390 binding to striatal D-1 DA receptors. By autoradiography, the increase of striatal [3H] SCH 23390 binding to D-1 DA receptors after chronic estradiol treatment was found to be homogenously distributed in this brain region. Thus, chronic treatment with estradiol of ovariectomized rats leads to an increased density of striatal D-1 DA receptors but, this hormonal modulation of D-1 DA receptors is lost when treatment is started 2 weeks after ovariectomy or later.

Animals↗

Endocrine and neurochemical actions of cocaine.

The endocrine and neurochemical actions of cocaine in human and animal studies are reviewed. In humans, cocaine has been shown to influence plasma prolactin and growth hormone, as well as the dexamethasone suppression of cortisol and the thyroid-stimulating hormone response to thyroid-releasing hormone. In rats, cocaine affects plasma prolactin, luteinizing hormone, and testosterone, and can lead to adrenocortical hypertrophy. Behavioral sensitization to cocaine in rats has been shown to be related to the gender of the animals and appears to be modulated by vasopressin. A review of the neurochemical actions of cocaine indicates the important role of dopamine systems in the euphoric effects of the drug, as well as its withdrawal symptoms. Cocaine is a potent dopamine uptake inhibitor, as shown by its competition with [3H]GBR-12935 (a specific ligand for the dopamine uptake sites) for striatum binding sites. However, it does not acutely affect the high-affinity agonist sites of the D-2 dopamine receptors, which are suggested to be the active form of the presynaptic receptor. Using microdialysis techniques, cocaine is shown to rapidly cause a large increase of rat striatal dopamine levels, while its metabolites dihydroxyphenylacetic acid and homovanillic acid are slightly decreased and increased, respectively.

Animals↗

Rapid conversion of high into low striatal D2-dopamine receptor agonist binding states after an acute physiological dose of 17 beta-estradiol.

Ovariectomized female rats injected with 17 beta-estradiol (100 ng, s.c.) showed, as previously observed, an increase of the dopamine (DA) metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) with no change of DA concentrations in the striatum. This increase was observed as soon as 15 min following the injection while plasma estradiol reached a peak of 78 pg/ml after 5 min and was significantly elevated until 45 min to ultimately return to control values at 60 min. We observed no significant change of the inhibition constants of high- and low-affinity D2 DA agonist binding sites and of the sum of high + low agonist DAergic agonist binding densities as detected by apomorphine competition of [3H]spiperone binding. By contrast, a significant conversion of high into low agonist affinity binding states was seen at 15 min (38.6% of conversion, P less than 0.05) and 30 min (40.0% of conversion, P less than 0.01) after the acute physiological steroid injection. Thus, very small doses of estradiol were able to rapidly increase DA turnover and modulate the striatal agonist affinity states of the D2 DA receptor. This effect of estradiol is probably non-genomic, presynaptic and may involve a membrane effect at the DA autoreceptor level.

3,4-Dihydroxyphenylacetic Acid↗

Sodium and guanine nucleotide regulation of dopamine receptor agonist and antagonist binding sites in MtTW15 pituitary tumors.

The modulation of the dopamine receptor in MtTW15 tumors was investigated. The antagonist dopaminergic binding site in MtTW15 tumors labelled with [3H]spiperone remains unchanged at 25 degrees C in the presence or absence of sodium or guanine nucleotides (Gpp(NH)p); by contrast at 37 degrees C sodium increases the affinity while Gpp(NH)p decreases it slightly. The dopamine receptor in this tumor, such as the intact adenohypophysis, exists in a high and low affinity state for dopamine agonists. These agonist affinity states evaluated with apomorphine competition for [3H]spiperone binding show similar affinities as those of intact tissue but have a lower proportion of the high affinity state. At 25 degrees C, a partial conversion of the high into the low affinity state is obtained in the presence of both sodium and Gpp(NH)p, while at 37 degrees C a complete conversion is observed. These data show differences in the modulation of antagonist and agonist dopaminergic binding sites in MtTW15 pituitary tumors compared with the intact pituitary.

Animals↗

A physiological dose of progesterone affects rat striatum biogenic amine metabolism.

Ovariectomized rats injected with progesterone (50 micrograms s.c.) showed a peak in striatum dopamine (DA) concentration after 15 min followed by a decrease at 60-75 min and a return to control values 90 min after the steroid injection. The DA metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were increased after the progesterone injection, with a peak at 45 min and a return to control values after about 2 h. Striatum serotonin (5-HT) concentrations remained unchanged after the progesterone injection while its metabolite 5-hydroxyindoleacetic acid (5-HIAA) was increased at 45 min and returned to control values after 2 h. The peak plasma progesterone concentration occurred 15-30 min after the steroid injection while estradiol concentrations were unchanged indicating no significant conversion of progesterone into estradiol. A similar experiment was performed in male rats. As with female rats, a progesterone injection led to a progesterone peak at 30 min while plasma estradiol levels remained unchanged. Male rats responded to the progesterone injection with a maximal increase of DA, DOPAC and HVA concentrations as soon as after 15 min and these amines remained elevated up to 75 min after the steroid injection. 5-HT and 5-HIAA remained unchanged after the progesterone injection. Thus, very small physiological doses of progesterone can increase striatum dopaminergic activity in rats of both sexes while serotonergic activity is influenced only in female rats. This effect is seen within minutes and is relatively short. It is probably non-genomic, presynaptic and similar to the effect of a small dose of a DA releasing agent.

3,4-Dihydroxyphenylacetic Acid↗

A comparative trial of ranitidine 300 mg at night with ranitidine 150 mg twice daily in the treatment of duodenal and gastric ulcer.

A multicenter double-blind comparative trial of oral ranitidine, 300 mg hs versus 150 mg bid, was conducted in 89 patients with duodenal ulcer (DU) and 54 with gastric ulcer (GU). Antacid tablets were prescribed prn. After 4 wk of treatment there were no statistically significant differences in the ulcer healing rates associated with the once daily (DU 86.4%, GU 62.5%) and the twice daily (DU 84.4%, GU 73.3%) regimens. Antacid consumption, by both DU and GU patients, was higher in the 150 mg bid group, but the differences did not achieve statistical significance. Further improvement in cumulative healing rates in response to both treatment regimens was observed following a second 4-wk treatment for those patients whose ulcers had failed to heal during the 1st month. Smoking adversely affected the rate of ulcer healing in DU patients, but had no significant effect on GU healing. No serious adverse effects or biochemical abnormalities were observed. Ranitidine 300 mg hs appears to be equally safe and effective as the standard regimen of 150 mg bid in the short-term treatment of uncomplicated gastroduodenal ulcer.

Adult↗

Effect of ranitidine on healing of peptic ulcer: a 2-month study.

A multicenter trial of oral ranitidine 150 mg bid was conducted in 41 patients with duodenal and 30 with gastric ulcers. Patients were randomly allocated in double-blind fashion to 4 wk treatment with either ranitidine or placebo, after which all unhealed patients were given 4 wk on the active drug without breaking the original allocation code. After 4 wk of treatment the healing rate associated with ranitidine was significantly superior to that of placebo in both duodenal and gastric ulcer patients. Further improvement in cumulative healing rates was observed after the 2nd month of the study. After the allocation code was broken and all patients had had the opportunity of up to 8 wk on the active drug, there remained only a single unhealed pyloric ulcer. No serious adverse effects or biochemical abnormalities were observed. Ranitidine is a potent and well-tolerated H2 antagonist. Therapy for 4 or 8 wk is highly effective in the treatment of uncomplicated gastroduodenal ulcer.

Adult↗