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Selective increase of dopamine D3 receptor gene expression as a common effect of chronic antidepressant treatments

Molecular Psychiatry volume 5, pages 378–388 (2000)Cite this article

Abstract

The mesolimbic dopaminergic system is a neuroanatomical key structure for reward and motivation upon which previous studies indicated that antidepressant drugs exert a stimulatory influence, via still unknown neurobiological mechanisms. Here we examined the effects of chronic administration of antidepressants of several classes (amitriptyline, desipramine, imipramine, fluoxetine and tranylcypromine) and repeated electroconvulsive shock treatments (ECT) on dopamine D3 receptor expression in the shell of the nucleus accumbens, a major projection area of the mesolimbic dopaminergic system. Short-term drug treatments had variable effects on D3 receptor mRNA expression. In contrast, treatments for 21 days (with all drugs except fluoxetine) significantly increased D3 receptor mRNA expression in the shell of nucleus accumbens; D3 receptor binding was also significantly increased by amitriptyline or fluoxetine after a 42-day treatment. ECT for 10 days increased D3 receptor mRNA and binding in the shell of nucleus accumbens. D1 receptor and D2 receptor mRNAs were increased by imipramine and amitriptyline, but not by the other treatments. The time-course of altered D3 receptor expression, in line with the delayed clinical efficiency of antidepressant treatment, and the fact that various antidepressant drugs and ECT treatments eventually produced the same effects, suggest that increased expression of the D3 receptor in the shell of nucleus accumbens is a common neurobiological mechanism of antidepressant treatments, resulting in enhanced responsiveness to the mesolimbic dopaminergic system.

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Author notes

  1. C-H Lammers

    Present address: Zentrum für Nervenheilkunde, Klinik für Neurologie, Rudolf-Bultmann Str 8, Marburg, 35039, Germany

  2. C-H Lammers and J Diaz: These two authors have contributed equally to this paper

Authors and Affiliations

  1. Laboratoire de Physiologie, Université René Descartes, 4 Avenue de l'Observatoire, Paris, 75006, France

    C-H Lammers & J Diaz

  2. Unité de Neurobiologie et Pharmacologie Moléculaire (U. 109) de l'Institut National de la Santé et Recherche Médicale, Centre Paul Broca, 2ter rue d'Alésia, Paris, 75014, France

    J-C Schwartz & P Sokoloff

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  1. C-H Lammers
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  2. J Diaz
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See also the Image page, Molecular Psychiatry 2000; 5: 229

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Lammers, CH., Diaz, J., Schwartz, JC. et al. Selective increase of dopamine D3 receptor gene expression as a common effect of chronic antidepressant treatments. Mol Psychiatry 5, 378–388 (2000). https://doi.org/10.1038/sj.mp.4000754

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