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J Costentin

Publications and source records attributed to J Costentin.

226 records · Page 13Linked to original sources
PubMedDate not supplied

MU and delta opioid receptors control differently the horizontal and vertical components of locomotor activity in mice.

The present study investigated the role of mu and delta opioid receptors in the control of the horizontal and vertical components of locomotion. Mice received intracerebroventricularly (i.c.v.) enkephalin analogs specific for either the mu or delta opioid receptors. The administration of the specific mu agonist [D-Ala2-NMePhe4-Gly5(ol)] enkephalin (DAGO) induced a dose-dependent increase in horizontal activity and a decrease in vertical activity. The specific delta agonist [D-Pen2,D-Pen5] enkephalin (DPDPE) increased both components of motor activity. The opiate antagonist naltrexone reversed the effects of DAGO, but did not influence the effects of DPDPE on motor activity. The pretreatment with the delta opiate antagonist ICI 154, 129 completely reversed the effects of DPDPE on locomotion but antagonized only partially the effects of DAGO on locomotion. These results indicate that the two components of locomotor activity--horizontal and vertical activity--are modulated differently by the stimulation of mu or delta opioid receptors.

Animals↗
PubMedDate not supplied

Centrally administered [D-Trp11]neurotensin, as well as neurotensin protected from inactivation by thiorphan, modifies locomotion in rats in a biphasic manner.

Neurotensin injected intracerebroventricularly at the dose of 30 ng per rat was without intrinsic effect on locomotion. When associated with the enkephalinase inhibitor thiorphan (50 micrograms, intracerebroventricular) it decreased locomotor activity. On the contrary, the 3 micrograms dose of NT, which had a tendency to decrease locomotion, stimulated locomotor activity when associated with thiorphan (50 micrograms, intracerebroventricular). This effect was independent of endogenous enkephalins since it was not suppressed by a high dose of naloxone (2 mg/kg). Similarly, increasing doses of the enkephalinase-resistant peptide [D-Trp11]neurotensin had a biphasic effect on locomotion since doses lower than 60 ng were hypokinetic whereas higher doses were hyperkinetic. This latter effect was not modified by thiorphan. It was antagonized by the dopamine antagonist haloperidol (50 micrograms/kg, IP).

Amino Acid Sequence↗
PubMedDate not supplied

Inhibition of apomorphine-induced yawning and penile erection by neurotensin.

The yawns and penile erection elicited in rats by apomorphine (100 micrograms/kg SC) are dose-dependently suppressed by the enkephalinase-resistant analog of NT, [D-Trp11]NT, intracerebroventricularly (ICV) injected (10-120 ng per rat). This antagonistic effect was shared by NT (0.75-3 micrograms per rat) administered ICV. The yawns induced by pilocarpine (2 mg/kg IP) were similarly antagonized by [D-Trp11]NT (30-120 ng per rat). The enkephalinase inhibitor acetorphan (5 mg/kg IV) reduced in a naloxone (2 mg/kg, SC)-resistant manner the apomorphine-induced penile erection or yawning.

Animals↗
PubMedDate not supplied

[Pharmacological and molecular aspects of the regulation of eating behavior. With special reference to the role of catecholamines and effects of amphetamine].

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. Alpha-2 and beta adrenergic receptors as well as D1 and D2 dopaminergic receptors participate in these effects. Amphetamine, which is an indirect catecholaminergic agonist, mobilizes neuronal catecholamines and fosters their various effects. Moreover, it exercises direct effects by its association with sites borne by glycaemia-sensitive neurons. This target seems to be common to a wide variety of anorectic agents. They are thought to reproduce on this hypothalamic "glucostat" the effect of a high blood glucose level, thus triggering off signals of satiety. In this unifying hypothesis, the diverse pharmacological profiles these agents are known to possess would result from associated properties.

Amphetamine↗
PubMedDate not supplied

[Brain dopamine receptors. Interactions between D1 and D2 receptors, and dopamine mediated behaviour].

The review begins by a brief presentation of the present state of knowledge on the multiplicity of brain dopamine receptors. The molecular basis of their distinction is reported, as well as the most specific ligands for each receptors type: D1, D2 (their isoforms A and B), D3, the putative D4 and autoreceptors. Then the review focuses on the respective location of D1 receptors (mainly linked positively to an adenylate cyclase) and of so-called D2 (lacking precision for distinguishing D2, D3 or D4), at the cellular level. The theoretical aspects of the functional interactions between these D1 and D2 receptors suggest four possibilities: Antagonism, indifference, additive synergy and potentiation. The effects resulting from the simultaneous administration of either D1 and D2 dopamine agonists or D1 and D2 dopamine antagonists were considered on various behaviours or functions. The four predicted types of interactions were found: D1/D2 antagonism on thermoregulation, D1/D2 indifference on nociception, additive synergy on the traction test, on anorexia or on the latency of the acoustic startle response, and finally potentiation on stereotypies or climbing behaviour. These data are completed by many other reported in an abundant literature about these interactions, which appear as modalities of regulation: their alterations might take part in several pathological states.

Adenylyl Cyclases↗
PubMedDate not supplied

Simultaneous assessment of the opiate-induced modifications in the vertical and horizontal components of locomotor activity in mice.

The effects of some opiates on the horizontal and vertical components of locomotor activity in mice were measured in actometers fitted with photoelectric cells counting horizontal displacements and the striding over a low partition wall. Morphine and fentanyl, used at low doses which did not modify the horizontal locomotor activity, decreased the striding over of the partition wall. Such a dissociation was not observed with either kappa or sigma agonists which affected in the same way the two components of the locomotor activity: both components were inhibited by kappa agonists and slightly stimulated by the sigma agonist SKF 10047. Although the opiate-induced inhibition of the striding over was induced by low doses of morphine, relatively high doses of naloxone were necessary for its antagonism. This apparently difficult antagonism could result in fact from the sedation which appeared when morphine was associated with naloxone.

Animals↗
PubMedDate not supplied

[From gene to behavior, a new way for elaborating new psychotropic agents].

Traditionally, the screening of new neuropsychotropic agents started from the observation of behavioural effects resulting from the administration of a new chemical. Then, one tried to precise its mechanism of action. Since about a decade the way for discovering psychotropic agents tends to be inverse. It starts from the characterization of genes and investigates on their expression products which are new biological targets. Ligands for these targets are developed and then the effects resulting from their administration are considered. In this new strategy, we will consider the cloning of genes and their expression in cultured cells; the knock out of these genes by homologous recombination; the extinction of gene expression by antisense oligodeoxynucleotides; the concentration of behavioural phenotypes by selective breeding.

Behavior↗