Publications by authors named "Costentin J"

In mice rendered poikilothermic by a prior (18 h) subcutaneous administration of reserpine (3 mg/kg) the injection of the D1 dopamine agonist SKF 38393 in doses of 1 mg/kg or more increased dose-dependently, the body temperature. The D1 dopamine antagonist SCH 23390, administered subcutaneously, antagonized, with an ID50 of 16 micrograms/kg, the reversal by SKF 38393 of reserpine-induced hypothermia. The intracerebroventricular administration of 1 microgram per mouse of SKF 38393 was sufficient to elevate by about 7 degrees C the temperature of reserpinized mice.

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Acetorphan, a parenterally active enkephalinase inhibitor, induced dose-dependently a naloxone-reversible analgesia on the hot-plate jump test in DBA/2J (DBA2) mice but was devoid of effects in C57BL/6J (C57) mice. By contrast, acetorphan increased locomotion in both strains; however, the DBA2 strain was much more sensitive than C57 mice to the locomotor stimulant effect. The increased locomotion was antagonized by naloxone in both strains.

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The present study focuses on the changes of two biochemical markers of the striatal dopaminergic innervation evaluated after different postmortem storage periods of rat heads either at room temperature (21 degrees C) or at 4 degrees C: (i) the uptake of [3H]dopamine (DA) into striatal synaptosomes and (ii) the specific binding of [3H]GBR 12783, a selective ligand for the neuronal dopamine uptake sites, to a striatal membrane fraction. The uptake of [3H]DA was completely abolished after 24 and 72 h storage of the tissue at 21 degrees C and 4 degrees C, respectively, whereas in the same conditions, the binding of [3H]GBR 12783 was slightly decreased. The Km and Kd of these two processes were virtually unchanged after the different storage periods considered, whereas the Vmax and Bmax were markedly decreased.

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The development of the specific uptake of dopamine in the rat striatum during the early postnatal period is compared with the ontogenetic changes of the specific binding of (3H)GBR 12783 to the site of uptake inhibition. During maturation, the increase in the specific binding of (3H)GBR 12783 parallels the increase in the specific uptake of dopamine. (3H)GBR 12783 specific binding sites increase in number from day 1 postpartum until 40 days, when they reach the adult level.

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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.

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DBA2 mice show an erratic spontaneous climbing which is reduced by increasing doses of direct dopamine agonists (apomorphine up to 5 mg/kg, piribedil up to 20 mg/kg). Sustained stereotyped climbing occurs when animals are treated with L-dopa plus benserazide and dexamphetamine. In this strain, which is spontaneously insensitive to apomorphine-induced climbing, this behaviour progressively appeared in a stereotyped manner after repeated administrations of apomorphine (5 mg/kg).

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Labelling of central dopaminergic systems with the dopamine uptake inhibitor [3H]GBR12783 was performed in vivo in mice by i.v. injection of a tracer dose of the ligand (40 microCi) 1 h before sacrifice.

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We designed phethiol (1-amino-1-benzyl-2-mercaptoethane) as a potent and selective inhibitor of Zn-containing aminopeptidases. This compound inhibited purified aminopeptidase M (EC.3.

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All the dopamine agonists (apomorphine, dipropylamino-5,6-dihydroxytetrahydronaphtalene, piribedil, bromocriptine, CBM 36-733) tested in the 'behavioral despair' test performed in mice had a dose-dependent anti-immobility effect, with the exception of the D-1 dopamine agonist, SKF 38393. This effect occurred at doses that reduced locomotor activity and decreased colonic temperature. A profound hypothermia of the same amplitude resulted from the immersion in water of the control and apomorphine (Apo)-treated mice.

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The intracerebroventricular administration of neuromedin N (from 50 ng to 5 micrograms) elicited a dose- and time-dependent hypothermia in mice. Two aminopeptidase inhibitors, bestatin (50 micrograms) and puromycin (50 micrograms), the endopeptidase 24.11 inhibitor, thiorphan (10 micrograms), and the angiotensin-converting enzyme inhibitor, captopril (50 micrograms), were tested for their ability to potentiate the neuromedin N-induced hypothermia.

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Among the numerous endogenous substances involved in the regulation of feeding behaviours, the catecholamines are in the front rank. The numerous studies devoted to this aspect of catecholamines emphasize the importance and complexity of their intervention. Depending on the cerebral structures on which they act and on whether noradrenaline or dopamine are concerned, orexigenic or anorexigenic effects have been described.

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At 0 degrees C, when Na+ was the only cation present in the incubation medium, increasing the Na+ concentration from 3 to 10 mM enhanced the affinity of [3H]1-[2-(++di-phenylmethoxy)ethyl]-4-(3-phenyl-2-propenyl)piperaz ine [( 3H]GBR 12783) for the specific binding site present in rat striatal membranes without affecting the Bmax. For higher Na+ concentrations, specific binding values plateaued and then slightly decreased at 130 mM Na+. In a 10 mM Na+ medium, the KD and the Bmax were, respectively, 0.

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Neurotensin induced significant antinociceptive activity as measured in a variety of nociceptive tests 10 and 30 min following intracerebroventricular (i.c.v.

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Thiorphan and acetorphan, two potent inhibitors of enkephalinase (EC 3.4.24.

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To investigate whether endogenous enkephalins modulate locomotion we studied the effect of the systemic administration of acetorphan, a parenterally active "enkephalinase" inhibitor. Locomotor activity in mice and rats was considered as an index to the activity of mesolimbic dopaminergic neurons. Acetorphan injected i.

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In several pain models, tricyclic antidepressants (TCAs) have been shown to reduce nociception. In the present study, we evaluated the antinociceptive effect of metapramine (META) in 4 nociception tests: (1) the hot plate test; (2) the phenylbenzoquinone-induced writhing; (3) the tail flick test; and (4) the test of electrical stimulation of the tail. We further analysed, using META and clomipramine (CLOM), the eventual role of endogenous opioids in analgesia induced by TCAs.

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The relationships between various properties of inhibitors of enkephalinase (membrane metalloendopeptidase, EC 3.4.24.

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[3H]GBR 12783 (1,2-(diphenylmethoxy)ethyl-4-(3-phenyl-2-propenyl)-piperazine), a specific dopamine uptake inhibitor, was tested for in vivo central binding in mice. The difference between the striatal and cerebellar levels of radioactivity was maximal 1 hour after the i.v.

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When Na+ was the only cation present in the incubation medium used for the determination of the specific binding of [3H]GBR 12783 in rat striatal membranes, the Na+-dependence between 10 and 210 mM Na+ was not observed. In media with low (10 mM) or high (130 mM) Na+ concentration, mazindol and nomifensine competed with [3H]GBR 12783 for its specific binding site with the same affinities. With the exception of amineptine, all the tested catecholamine uptake inhibitors were equally potent to compete with [3H]GBR 12783 when Na+ concentration was decreased from 130 to 10 mM.

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The effects of amineptine on 3H-dopamine uptake and 14C-dopamine release have been studied simultaneously in double labelling test performed on rat striatal synaptosomes. 3H-dopamine uptake was completely inhibited at 10 microM amineptine, a concentration which produced only a weak 14C-DA release (13% of the 14C-radioactivity stored). The IC 50 for the inhibition of 3H-DA uptake was not modified by a previous treatment with reserpine whereas the IC 50 of (+) amphetamine and the IC 50 of clomipramine were decreased 9 fold and increased two fold, respectively.

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We labelled the neuronal dopamine uptake system by using the potent dopamine uptake inhibitor GBR 12783 in its tritiated form (18.3 Ci/mmol). The binding of [3H]GBR 12783 to rat striatal membranes was saturable and specific with a Kd of 1.

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Acetorphan, i.e. N-[(R,S)-3-acetylmercapto-2-benzylpropanoyl]-glycine, benzyl ester, is a lipophilic derivative of Thiorphan, a potent inhibitor of "enkephalinase" (EC 3.

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