Biomedical subjects

Jean Costentin

Publications and source records attributed to Jean Costentin.

41 records · Page 3Linked to original sources

PubMed2002

Mouse lines differing in sensitivity to beta-CCM differ in tasks used for testing antidepressants.

Two lines of mice, previously selected for their sensitivity (BS) or their resistance (BR) to an anxiogenic benzodiazepine (BZ) receptor inverse agonist, methyl beta-carboline-3-carboxylate (beta-CCM), have recently been shown to present several differences in anxiety. In the present study, attempt was made to extend their behavioral profile in two situations classically used for testing antidepressant drugs. Reassessment of locomotor performance of these new populations confirmed that the motor activity of BR mice was lower than that of BS mice. In both the forced-swimming and the tail suspension tests, the immobility time of BS mice was significantly higher than that of BR mice. In the tail suspension test, two administrations of imipramine (30 mg/kg i.p., 5 h and 30 min before testing) significantly reduced the immobility time of BS mice but not of BR mice. From these data, it appears that BS mice are more "depressed" than BR mice. Thus, these selectively bred lines may represent potentially useful animal models to investigate behavioral, neurochemical and neuroendocrine correlates of antidepressant action.

Animals↗

PubMed2002

[Recent neurobiological data on cannabis].

The alarming increase in cannabis abuse has triggered a renewed interest in the neurobiological mechanisms which underlie its effects, particularly as regards its addictive properties either intrinsic or when crossed with other narcotics as well as its subsequent damage. We here report an evaluation of experimental data which reveal in animals a psychological dependence, common to all addictive drugs; a physical dependence, which is considered up to now as the characteristic of "hard addictive drugs"; the incentive effect that cannabis should exert on the inclination to abuse other addictive drugs, especially heroin; and finally the close relationships which seem to exist between cannabis and schizophrenia. Most of these recent data are far from reassuring as regards cannabis psychotoxicity. Furthermore they underline its potential danger and prompt increased caution.

Cannabinoids↗

PubMed1990

Acetorphan, an Enkephalinase Inhibitor, Modulates Dopaminergic Transmission in Rat Olfactory Tubercle, but not in the Nucleus Accumbens and Striatum.

The present study focused on the effects of acetorphan, a parenterally active enkephalinase inhibitor, on dopaminergic transmission in rat olfactory tubercle, nucleus accumbens and striatum. Acetorphan was administered i.v. (10 mg/kg) 15 min before measurement of the in vivo specific binding of [3H]N-propylnorapomorphine ([3H]NPA) or measurement of the levels of dopamine (DA) and its metabolites 3-methoxytyramine-homovanillic acid (3MT-HVA) in the three areas. Acetorphan decreased the in vivo specific binding of [3H]NPA in the olfactory tubercle, this effect being antagonized by naloxone 1.5 mg/kg s.c. DA release in this brain structure was also significantly increased by acetorphan 10 mg/kg, as indicated by the 3MT:DA and HVA:DA ratios. Neither the specific binding of [3H]NPA nor DA metabolism and release were modified by the inhibitor in the striatum and the nucleus accumbens. The stimulant effect of acetorphan was significantly decreased in rats in which a bilateral lesion of dopaminergic endings in the olfactory tubercle had been produced by 6-hydroxydopamine (6-OHDA). These results suggest that dopaminergic transmissions in the olfactory tubercle are particularly sensitive to the modulation exerted by endogenous enkephalins, this modulation being at least partly involved in the increased locomotion induced by the enkephalinase inhibitor.

Journal Article↗

PubMed1987

Analgesic effects of metapramine and evidence against the involvement of endogenous enkephalins in the analgesia induced by tricyclic antidepressants.

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. The analgesic effects of META and CLOM in the hot plate test and in the test of electrical stimulation of the tail were reversed by naloxone. On the other hand, we failed to demonstrate a potentiation of META- or CLOM-induced analgesia by acetorphan, an inhibitor of 'enkephalinase.' We also failed to show a potentiation of Met5-enkephalin intracerebroventricularly injected by the two TCAs. Moreover, the administration of the enzymatic inhibitor or of Met5-enkephalin led to a slight decrease of the analgesic effect of the TCAs. These results (1) indicate that in our 4 pain tests, META clearly reduces nociception and (2) provide evidence that the involvement of endogenous enkephalins in the analgesia induced by TCAs is improbable.

Animals↗

PubMedDate not supplied

[The importance of in vivo pharmacology in fundamental research on psychotropic drugs and their biological targets].

The main families of psychotropic drugs have been almost fortuitously discovered, from investigations carried out directly in humans. The burst of studies triggered by these discoveries and the considerably strengthened ethical guidelines for clinical trials have allowed remarkable developments in preclinical studies performed in animals, and especially in rodents. The corresponding models may be classified as follows: homologous models mimicking the aetiology of the disease against which one attempts to develop drugs; isomorphic models mimicking specific symptoms of a disease but involving different aetiological mechanisms; predictive models, which assess the effect of a drug on behavioural or other functional signs/symptoms unconnected to the psychiatric disease but involving the same type of biological targets as those affected by the disease; and theoretical or explanatory models that aim to elucidate the mechanism of action of agents producing psychotropic effects. Among the latter, the following can be cited: the knock out of genes coding for a specific biological target; the neutralisation of a specific ARNm by antisense oligodeoxynucleotides, which also aims to prevent the synthesis of a specific biological target; use of controlled reproduction to achieve a concentration of genes, the association of which leads to the development of a disease. Each one of these approaches has been illustrated by an example developed within the Rouen Neuropsychopharmacology Unit: the psychobehavioural spectrum of mice with invalidation of the gene coding for adenosine A2A receptors; the abolition of either nociceptin ORL1 receptors or neurotensin NTR2 receptors in order to characterise their functions; the concentration, by controlled breeding in mice, of a phenotype corresponding to that of depression. These developments illustrate several recent developments in neuropsychopharmacology with the aim of emphasising the vitality of this discipline.

Animals↗