Biomedical subjects

B Naudin

Publications and source records attributed to B Naudin.

7 recordsLinked to original sources

PubMed2002

Nociceptin/orphanin FQ and related peptides reduce the increase in plasma corticosterone elicited in mice by an intracerebroventricular injection.

Nociceptin/orphanin FQ (=N/OFQ), the endogenous ligand of ORL1 receptor (=NOP), has been reported to induce, in rodents, after intracerebroventricular (i.c.v.) administration, anti-stress and anxiolytic effects. We have observed that the handling of mice followed by an i.c.v. injection of saline, induced a marked increase in the plasma corticosterone level (+250%) measured 30 minutes later. When N/OFQ was injected intracerebroventricularly, using a 1 microg dose, the increase in plasma corticosterone was significantly lower than in saline injected mice. N/OFQ(1-13)NH(2), known as a NOP receptor agonist, at the same 1 microg dose, also induced a lesser increase in plasma corticosterone level than a saline i.c.v. injection. The pseudopeptide [Phe(1)-psi(CH(2)-NH)Gly(2)]N/OFQ(1-13)NH(2), defined either as an agonist or an antagonist of NOP receptor, at the 0.1 microg dose, behaved in a similar manner as N/OFQ, by decreasing the plasma corticosterone level. Finally, [Nphe(1)]N/OFQ(1-13)NH(2), although presumed to be a selective NOP receptor antagonist, also decreased the corticosterone level at the 0.1 microg dose. These observations suggest the implication of N/OFQ in the regulation of response to stress, through an action on the hypothalamo-pituitary-adrenocortical axis. Moreover, they evidence a similar effect of N/OFQ and N/OFQ(1-13)NH(2), but also of two other related peptides displaying antagonist properties on NOP receptors. These data suggest that several subtypes of N/OFQ receptors could exist.

Animals↗

PubMed1998

Behavioural and neurochemical evidence that the antimicrobial agent oxolinic acid is a dopamine uptake inhibitor.

The antimicrobial agent oxolinic acid, injected i.p. in mice, induced a dose dependent increase in locomotor activity. This stimulation culminated at the 32 mg/kg dose and became smaller for higher doses (64-128 mg/kg). When opposed to increasing doses (50-100-200 microg/kg i.p.) of haloperidol (D2 dopamine receptor antagonist), the stimulant locomotor effect of 32 mg/kg oxolinic acid was not significantly reversed. On the contrary increasing doses (7.5-15-30 microg/kg s.c.) of SCH 23390 (D1 dopamine receptor antagonist) inhibited the stimulant locomotor effect. In mice made completely akinetic by a pretreatment with reserpine (4 mg/kg s.c., 18 h before testing), dexamphetamine (2 mg/kg s.c.) reversed this akinesia and even displayed a stimulant activity, similar to that observed in mice not treated by reserpine. On the contrary, oxolinic acid (32 mg/kg) did not reverse the reserpine induced akinesia and even opposed the reversion induced by dexamphetamine. In a synaptosomal fraction prepared from striatum of rats, oxolinic acid inhibited the 3H dopamine uptake with an IC50 = 4.3+/-0.6 x 10(-6) M. Finally, in mice injected i.v. with a tracer dose of 3H WIN 35428 (1 microCi) (a dopamine uptake blocker), 32 mg/kg oxolinic acid, i.p. administered, reduced by about 50% the specific binding of the radioligand to striatal dopamine carriers. It is concluded that the stimulant locomotor effect of oxolinic acid depends on the blockade of the neuronal dopamine uptake complex.

Animals↗

PubMed1995

Acute L-DOPA pretreatment potentiates 6-hydroxydopamine-induced toxic effects on nigro-striatal dopamine neurons in mice.

We have studied the effect of various agents on the decreases in striatal levels of dopamine (DA) and its metabolites which were observed 14 days after an intracerebroventricular (i.c.v.) administration of 50 micrograms 6-hydroxydopamine (6-OHDA) to mice. A pretreatment of mice with either a tyrosine hydroxylase inhibitor (alpha-methyl-p-tyrosine), a D2 receptor agonist (bromocriptine) or antagonist (haloperidol), or a vesicular uptake inhibitor (tetrabenazine) did not modify the 6-OHDA-induced decreases in DA and metabolites, indicating that DA synthesis, vesicular storage and neuronal firing rates are not mainly involved in the 6-OHDA-induced toxicity on the DA neurons. Conversely, a pretreatment with L-DOPA + benserazide potentiated the 6-OHDA-induced decreases in striatal levels of DA, homovanillic acid and 3-methoxy-tyramine. This effect was not due to an increased 6-OHDA uptake via the neuronal carrier since a pretreatment with L-DOPA + benserazide, performed 1-1.5 h before sacrifice, decreased the apparent affinity of the uptake, an effect which disappeared when considering the total DA concentration present in incubation medium ([3H]DA and cold released DA). In conclusion, potentiation of the 6-OHDA neurotoxicity by L-DOPA rises again the important problem of the safety of the latter drug in therapeutics.

Animals↗

PubMed1992

Prevention by Ginkgo biloba extract (EGb 761) and trolox C of the decrease in synaptosomal dopamine or serotonin uptake following incubation.

Prolonged incubation of synaptosomes in Krebs-Ringer oxygenated medium in the presence of ascorbic acid (10(-4) M) led, after 20 min, to a decrease in [3H]dopamine (DA) (synaptosomes prepared from the striatum) and [3H]serotonin (5HT) (synaptosomes prepared from the cortex) uptake. The decrease was progressive and uptake was virtually abolished after a 60 min incubation period. A concentration-dependent (from 5 x 10(-6) M) role of ascorbic acid in the decrease of [3H]DA or [3H]5HT uptake was demonstrated. This decrease was potentiated by Fe2+ ions and prevented by the ferrous chelating agent desferrioxamine. Thus, the progressive decrease in synaptosomal uptake of either [3H]DA or [3H]5HT could depend on the generation of free radicals by the association of ascorbic acid with Fe2+ ions. The decrease in synaptosomal uptake was prevented, in a concentration-dependent manner, by the Ginkgo biloba extract EGb 761 (4-16 micrograms/mL) and the vitamin E analog trolox C (10(-4) M). The terpenic fraction of EGb 761, Bn 52063 (up to 0.5 microgram/mL), did not prevent the reduction of [3H]amine uptake. In contrast, the flavonoidic fraction, Cp 202, was effective (from 1 microgram/mL) and its efficacy was shared by the flavonoid quercetin (from 0.1 microgram/mL). The prolongation of the ability of synaptosomes to take up [3H]amine elicited by EGb 761, in particular its flavonoidic fraction, as well as by trolox C could be due to their free radical scavenger properties.

Animals↗

PubMed1991

Influence of oxygen availability on the neurotoxic effect of 6-hydroxydopamine on nigro-striatal dopaminergic neurons.

The neurotoxin 6-hydroxydopamine (6-OHDA) was intracerebroventricularly injected (50 micrograms per mouse) in mice submitted to various oxygenation conditions and the striatal levels of dopamine (DA) and its metabolites were determined by HPLC 7 days later. In normoxic conditions the striatal depletion in DA reached 50%. This effect was not modified by a normobaric hypoxia (10% O2) applied 30 min before and 30 min after the 6-OHDA injection. On the contrary, the neurotoxic effect was reduced when the hypoxia was prolonged up to 11 h after the drug administration. When a normobaric hyperoxia (60% O2) was applied 30 min before and 11 h after the 6-OHDA injection, the neurotoxic effects of the latter were not modified. These data, as well as other results obtained from ex vivo experiments showing that normobaric hypoxia or hyperoxia did not modify the striatal synaptosomal [3H]DA uptake, indicate that oxygen availability does not exert a critical influence on the efficiency of the neuronal dopamine uptake complex.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1990

Effects of various direct or indirect dopamine agonists on the latency of the acoustic startle response in rats.

The effects of dopamine agonists were investigated on the latency of the acoustic startle response in male Wistar rats. Four indirect dopamine agonist were tested: GBR 12783 (5-20 mg/kg), BTCP (5-20 mg/kg), dexamphetamine (3-6 mg/kg) and L-DOPA 100 mg/kg associated with benserazide 25 mg/kg; they induced an increase in startle latency. Apomorphine at a dose (50 micrograms/kg) known to decrease dopaminergic transmissions, was ineffective on the startle response. On the contrary, at 0.6 or 2 mg/kg, apomorphine induced an increase in the startle latency. A similar effect was observed with bromocriptine at 10 mg/kg from the 10th min up to at least the 9th hour after treatment. The specific agonist of D2 receptors Ru 24926 (0.45 mg/kg) enhanced the startle latency as well as the specific agonist of D1 receptors SKF 38393 (10 mg/kg). The association of these drugs resulted in an apparent additivity of their individual effects. The effect of apomorphine (0.6 mg/kg) was only partially reduced by a high dose of the specific D2 antagonist amisulpride (80 mg/kg) and more clearly antagonized by the specific D1 antagonist SCH 23390 (50 micrograms/kg). It is concluded that D2 and D1 receptors contribute to the increase in startle latency elicited by direct or indirect dopamine agonists.

Acoustic Stimulation↗

PubMed1989

Characteristics of the dopamine receptors involved in the anorectic effects of apomorphine in mice.

In food-deprived mice apomorphine injected SC induced a brief (15-30 min) dose-dependent (30-150 micrograms/kg) reduction in food intake. This effect occurred in naive mice as well as in mice habituated to a food deprivation procedure. The anorectic effect of apomorphine (150 micrograms/kg SC) was antagonized by sulpiride (ID50 = 8.6 mg/kg) and by haloperidol (ID50 = 66 micrograms/kg) but domperidone was ineffective (250 micrograms/kg). Mice submitted to a semi-chronic (6 d) blockade of dopamine receptors by haloperidol or injected intracerebroventricularly with 125 micrograms 6-hydroxydopamine 21 d before testing failed to develop a hypersensitivity to the anorectic effect of apomorphine (60 micrograms/kg). Although a single apomorphine injection (5 mg/kg) induced tolerance to the hypothermic effect of a second apomorphine injection of 150 micrograms/kg, it did not modify the anorectic effect. Repeated apomorphine injection (5 x 5 mg/kg) resulted in a slight but significant reduction in apomorphine-induced anorexia. A similarly significant reduction was not observed in mice submitted to repeated injections of dexamphetamine (5 x 5 mg/kg).

Animals↗