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Etude des mécanismes neurobiologiques de la dépendance aux opiacés

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Résumé

Les mécanismes neurobiologiques de la dépendance aux opiacés, comme pour toutes les drogues addictives, sont mal connus.

Les effets de renforcement positif des opiacés (effets «hédoniques»), tenus pour responsables de la dépendance psychique, impliquent les récepteurs opiacés de l'aire tegmentale ventrale et du noyau accumbens, ainsi que l'activation du système dopaminergique mésolimbique. Mais d'autres structures sont également en cause.

Lors d'une consommation prolongée les circuits neurobiologiques du renforcement positif sont le siège de phénomènes adaptatifs, opposés aux effets des opiacés, et responsables de la tolérance ainsi que des effets aversifs du sevrage.

Les opiacés ont en outre des effets de renforcement négatif (sédation de la douleur morale) dont le substratum neurobiologique n'est pas connu.

Les structures (substance grise périaqueducale, Locus Coeruleus, complexe amygdalien) et les mécanismes de la dépendance physique sont différents de ceux du renforcement positif.

Au niveau des neurones exposés de manière prolongée aux opiacés on peut également observer tolérance et/ou dépendance.

La spécificité régionale de ces phénomènes cellulaires, leur possible dissociation, leurs mécanismes précis ne sont pas expliqués.

En outre deux questions fondamentales restent posées:

  • • Comment les réseaux neuronaux de la dépendance physique et ceux de la dépendance psychique encodent-ils ces phénomènes comportementaux à partir des signaux élémentaires, cellulaires, que leurs délivrent les récepteurs opiacés?

  • • Pourquoi tolérance et dépendance sont-elles le fait des consommations toxicomaniaques d'opiacés et ne s'observentelles pas lorsqu'ils sont correctement utilisés comme analgésiques?

Summary

The neurobiological basis for dependence on opiates, as for all the other addictive drugs, is not well known.

The positive reinforcement effects (or «hedonic» effects), considered as accountable for psychical dependence, involve opiates receptors in Tegmental Ventral Area and Nucleus Accumbens and activation of the mesolimbic dopaminergic pathway. But other structures are concerned.

For a sustained consumption, adaptative processes expand in the circuits of positive reinforcement, opposite of the opiates effects and they are accountable for tolerance and adversive effects of withdrawal.

Moreover opiates have direct effects of negative reinforcement (sedation of moral pain) for which the neurobiological substratum is unknown.

Structures (Locus Coeruleus, amygdaloid complex, Periaqueducal Gray) and mecanisms of physical dependence are different from these of positive reinforcement.

At neuronal level, dependence and/or tolerance can be observed. But their precise mecanisms, their possible dissociation, their regional specificity remain unexplained.

Two essential questions have still no answers

  • • How do the circuits of positive reinforcement and physical dependence encode these behaviors from cellular signals mediated by opiates receptors?

  • • Why are tolerance and dependence only observed when opiates are used by drug addicts and not when they are correctly prescribed to pain patients?

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Correspondence to H. Ollat.

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Ollat, H. Etude des mécanismes neurobiologiques de la dépendance aux opiacés. Doul. et Analg. 2, 51–60 (1989). https://doi.org/10.1007/BF03013057

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Key words

  • Opiates
  • tolerance
  • dependence
  • reinforcement
  • withdrawal
  • neurobiological bases