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Évolution des idées sur le mécanisme d'action des antidépresseurs : le concept d'hétéro-régulation des récepteurs

Published online by Cambridge University Press:  28 April 2020

J.P. Tassin
J.P. Tassin*
Affiliation:
Chaire de Neuropharmacologie, INSERM U.114, Collège de France - 75231, PARIS CÉDEX 05
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Résumé

Des lès premières années d'utilisation clinique des antidépresseurs, les neurones à sérotonine (5-HT) et à noradrénaline (NA) ont été considérés comme les sites d'action privilégiés de ces médicaments.

En vingt ans, les idées sur leurs mécanismes d'action ont évolué parallèlement à la progression des connaissances et à l'obtention de nouvelles molécules actives :

  • - Tout d'abord, les effets présynaptiques des traitements aigus (inhibition des monoamines oxydases et inhibition de la recapture des monoamines par les antidépresseurs tricycliques) ont paru expliquer l'effet clinique de ces substances.

  • - Plus tard, les effets post-synaptiques des traitements chroniques (désensibilisation des récepteurs β-adrénergiques et, dans la plupart des cas, la désensibilisation des récepteurs 5-HT2) se sont avérés être une action biochimique commune de ces traitements.

  • - Récemment, les effets synaptiques homologues - en l'occurrence la desensibilisation des récepteurs α2-adrénergiques - ont été considérés comme un préalable à la désensibilisation des récepteurs β-adrénergiques post-synaptiques.

  • - Enfin, les effets synaptiques hétérologies sont proposés comme pouvant rendre compte de Taction clinique des antidépresseurs.

C'est la stimulation - directe ou indirecte - des récepteurs sérotoninergiques (5-HT2) qui serait nécessaire à l'obtention d'un découplage β lors d'une stimulation des récepteurs β-adrénergiques.

Les molécules antidepressives n'auraient d'action thérapeutique qu'à condition d'agir de façon synergique sur les transmissions sérotoninergique et noradrénergique.

Summary

Summary

During the first years of clinical use of anti-depressants, serotonergic (5-HT) as well as noradrenergic (NA) neurons were considered as the privileged sites of action of these drugs.

For the last twenty years, ideas on their mechanism of action have progressed in parallel with an increased scientific knowledge and the availability of new active molecules.

- First, the presynaptic effects of acute treatments (monoamine oxidases inhibition and inhibition of the monoamine reuptake by tricyclic anti-depressants) seemed to explain the clinical effect of these substances.

- Later, the postsynaptic effects of chronic treatments (desensitization of β-adrenergic receptors and, in most cases, the desensitization of 5-HT2 receptors) were considered as being the common biochemical sites of these treatments.

- Recently, the effects on homologous synapses - i.e. the desensitization of the α2 adrenergic receptors - seemed to be necessary for the further desensitization of the postsynaptic β-adrenergic receptors.

- Finally, the effects on heterologous synapses are proposed as sustaining the clinical action of anti-depressants.

It is the stimulation - direct or indirect - of serotonergic receptors (5-HT2) which would be necessary to obtain the uncoupling of the β-receptors following their hyperstimulation.

The anti-depressive molecules would not, therefore, perform their therapeutic effect without acting in a synergistic manner on serotonergic and noradrenergic transmissions.

Keywords

AntidépresseursRécepteurs sérotoninergiquesRécepteurs noradrénergiquesHétéro-régulation des récepteurs
Type
Research Article
Information
Psychiatry and Psychobiology , Volume 1 , Issue 1 , 1986 , pp. 62 - 74
Copyright
Copyright © European Psychiatric Association 1986

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References

Bibliographie/References

Barbaccia, ML, Brunello, N, Chuang, DM & Costa, E - On the mode of action of imipramine : relationship between serotonergic axon terminal function and down-regulation of βadrenergic receptors. Neuropharmacology 1983; 22: 373–383.CrossRefGoogle Scholar
Baudry, M, Martres, MP & Schwartz, JC - Modulation in the sensitivity of noradrenergic receptors in the CNS studied by the responsiveness of the cyclic AMP system. Brain Res 1976; 116:111–124.CrossRefGoogle ScholarPubMed
Bevan, P, Bradshaw, CM & Szabadi, E - Effects of iprindole on responses of cortical and caudate neurones to monoamines and acetylcholine. Br J Pharmacol 1975; 55: 17–25.CrossRefGoogle ScholarPubMed
Blackshear, MA & Sanders-Bush, E - Serotonin receptor sensitivity after acute and chronic treatment with mianserin. J Pharmac Exp Ther 1982; 221: 303–308.Google ScholarPubMed
Brodie, BB, Pletscher, A & Shore, PA - Serotonin-releasing activity limited to Rauwolfia Alkaloids with tranquilizing action. Science 1956; 123:992.CrossRefGoogle ScholarPubMed
Brunello, N, Barbaccia, ML, Chuang, DM & Costa, E - Down-regulation of β-adrenergic receptors following repeated desmethylimipramine injections : permessive role of serotonergic axons. Neuropharmacology 1982; 21: 1145–1149.CrossRefGoogle ScholarPubMed
Bunney, WE & Davis, JM - Norepinephrine in depressive reactions. Arch Gen Psychiatr 1965; 13:483–494.CrossRefGoogle ScholarPubMed
Carlsson, A, Johansson, J, Lindqvist, M & Fuxe, K - Demonstration of extraneuronal 5-hydroxytryptamine accumulation in brain following membrane-pump blockade by chlorimipramine. Brain Res 1959; 12:456–460.CrossRefGoogle Scholar
Chneiweiss, H - Peptides et régulations du métabolisme intermédiaire dans le cortex cérébral. DEA de Pharmacologie Cellulaire, Université Paris VI, 1983.Google Scholar
Crews, FT & Smith, CB - Presynaptic alpha-receptor subsensitivity after long-term antidepressant treatment. Science 1978; 202:322–324.CrossRefGoogle ScholarPubMed
Dooley, DJ, Hanser, KL & Bittiger, H - Differential decrease of the central β-adrenergic receptor in the rat after subchronic infusion of desipramine and clenbuterol. Neurochem Int 1983; 5:333–338.CrossRefGoogle ScholarPubMed
Gandolfi, O, Barbaccia, ML & Costa, E - Comparison of iprindole, imipramine and mianserin action on brain serotonergic and beta-adrenergic receptors. J Pharm Exp Ther 1984; 229: 782–786.Google ScholarPubMed
Hamon, M - Intégration de la notion de récepteurs dans la pharmacologie des antidépresseurs. L'Encéphale 1981; VII: 381–396.Google Scholar
Janowsky, A, Okada, F, Monier, DH, Applegate, CD, Sulser, F & Steranka, LR - Role of serotonergic input in the regulation of the β-adrenergic receptor-coupled adenylate cyclase system. Science 1982; 218:900–901.CrossRefGoogle ScholarPubMed
Kellar, KJ & Bergstrom, DA - Electroconvulsive shock : effects on biochemical correlates of neurotransmitter receptors in rat brain. Neuropharmacology 1983; 22:401–406.CrossRefGoogle ScholarPubMed
Kelleher, DJ, Pessin, JE, Ruoho, AE & Johnson, GL - Phorbol ester induces desensitization of adenylate cyclase and phosphorylation of the β-adrenergic receptor in turkey erythrocytes. Proc Natl Acad Sci USA, 1984; 81:4316–4320.CrossRefGoogle ScholarPubMed
Langer, SZ - Physiological and pharmacological role of presynaptic receptor systems in neurotransmission. in : Presynaptic receptors. Adv in Biosci (Langer, SZ, Starke, K & Dubocovich, M eds). Vol. 18 Pergamon Press, Oxford, 1979.Google Scholar
Langer, SZ, Moret, C, Raisman, R, Dubocovich, ML & Briley, M - High-affinity 3H-imipramine binding in rat hypothalamus is associated with the uptake of serotonin but not norepinephrine. Science 1980; 210:1133–1135.CrossRefGoogle Scholar
Langer, SZ & Raisman, R - Binding of 3H-imipramjne and H-desipramine as biochemical tools for studies in depression. Neuropharmacology 1983; 22:407–413.CrossRefGoogle Scholar
Lee, CM & Snyder, SH - Norepinephrine neuronal uptake binding sites in rat brain membranes labeled with 3H-desipramine. Proc Natl Acad Sci USA, 1981; 78: 5250–5254.CrossRefGoogle ScholarPubMed
Maggi, A, U'Prichard, DC & Enna, SJ - Differential effects of antidepressant treatment on brain monoaminergic receptors. Eur J Pharmac 1980; 61: 91–98.CrossRefGoogle ScholarPubMed
Minneman, KP, Dibner, MD, Wolfe, BB & Molinoff, PB - Beta-1 and beta-2 adrenergic receptors in rat cerebral cortex are independently regulated. Science 1979; 204: 866–868.CrossRefGoogle Scholar
Mishra, R, Janowksy, A & Sulser, F - Action of mianserin and zimelidine on the norepinephrine receptor coupled adenylate cyclase system in brain : subsensitivity without reduction in βadrenergic receptor binding. Neuropharmacology 1980; 19: 983–987.CrossRefGoogle Scholar
Nishizuka, Y - The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature 1984; 308:693–698.CrossRefGoogle ScholarPubMed
Paul, SM & Crews, FT - Rapid desensitization of cerebral cortical βadrenergic receptors induced by desmethylimipramine and phenoxybenzamine. Eur J Pharmac 1980; 62:349–350.CrossRefGoogle Scholar
Peroutka, SJ & Snyder, SH - Long-term antidepressant treatment decreases spiroperidol-labelled serotonin receptor binding. Science 1980; 210:88–90.CrossRefGoogle ScholarPubMed
Racagni, G, Mocchetti, I, Calderini, G, Battistella, A & Brunello, N - Temporal sequence of changes in central noradrenergic system of rat after prolonged antidepressant treatment : receptor desensitization and neurotransmitter interactions. Neuropharmacology 1983; 22:415–424.CrossRefGoogle ScholarPubMed
Raisman, R, Briley, M & Langer, SE - Specific tricyclic antidepressant binding sites in rat brain. Nature 1979; 291:148–150.CrossRefGoogle Scholar
Raisman, R, Briley, MS & Langer, SZ - Specific tricyclic antidepressant binding sites in rat brain characterized by high affinity 3H-imipramine binding. Eur J Pharmac 1980; 61: 373–380.CrossRefGoogle Scholar
Reibaud, M, Blanc, G, Studler, JM, Glowinski, J & Tassin, JP - Non-DA prefronto-cortical efferents modulate Dl receptors in the nucleus accumbens. Brain Res 1984; 305:43–50.CrossRefGoogle Scholar
Reisine, T, Johnson, R, Wiech, N, Ursillo, R & Yamamura, HI - Rapid desensitization of central beta-receptors and up-regulation of α-2 receptors following antidepressant treatment. Adv Biochem Psychopharmacol 1982; 31: 63–67.Google ScholarPubMed
Schildkraut, JJ - The catecholamine hypothesis of affective disorders : a review of supporting evidence. Am J Psychiatr 1965; 122:509–522.CrossRefGoogle ScholarPubMed
Schramm, M & Selinger, Z - Message transmission receptor controlled adenylate cyclase system. Science 1984; 225: 1350–1356.CrossRefGoogle ScholarPubMed
Scott, JA & Crews, FT - Rapide decrease in rat brain β-adrenergic receptor binding during combined antidepressant α-2 antagonist treatment. J Pharmacol Exp Ther 1983; 224:640–644.Google Scholar
Scott, JA & Crews, FT - Adrenergic-serotonergic interactions in antidepressant action. Abstract, 5e séminaire hivernal des Neurosciences Européens, session 22, 1985.Google Scholar
Sulser, F, Janowsky, AJ, Okada, F, Monier, DH & Moliley, PL - Regulation of recognition and action function of the norepinephrine (NE) receptor-coupled adenylate cyclase system in brain : implications for the therapy of depression. Neuropharmacology 1983; 22:425–431.CrossRefGoogle ScholarPubMed
Tang, SW & Seeman, P - Effect of antidepressant drugs on serotonergic and adrenergic receptors. Naunyn Schmiedeberg's. Arch Pharmac 1980; 311:255–261.CrossRefGoogle Scholar
Tassin, JP, Simon, H, HERVÉ D, Blanc, G, LE MOAL M, Glowinski, J & Bockaert, J - Non-dopaminergic fibres may regulate dopamine-sensitive adenylate cyclase in the prefrontal cortex and the nucleus accumbens. Nature 1982; 295:696–698.CrossRefGoogle Scholar
U'Prichard, DC, Greenberg, DA, Sheenan, PP & Snyder, SH - Tricyclic antidepressants : therapeutic properties and affinity for α-noradrenergic receptor binding sites in the brain. Science 1978; 199: 197–198.CrossRefGoogle Scholar
Vetulani, J & Sulser, F - Action of various antidepressant treatments reduces reactivity of noradrenergic cyclic AMP generating system in limbic forebrain. Nature 1975; 257: 495–496.CrossRefGoogle ScholarPubMed
Widlocher, D, Lecrubier, Y, Jouvent, R, Puech, AJ & Simon, P - Antidepressant effect of salbutamol. Lancet 1977; 2:767–768.CrossRefGoogle ScholarPubMed
Wolfe, BB, Harden, TK, Sporn, JR, Molinoff, PB - Presynaptic modulation of beta-adrenergic receptors in rat cerebral cortex after treatment with antidepressants. J Pharmac Exp Ther 1978; 207:446–457.Google ScholarPubMed
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