Article Dans Une Revue European Journal of Neuroscience Année : 2000

Differential regulation of the dopamine D1, D2 and D3 receptor gene expression and changes in the phenotype of the striatal neurons in mice lacking the dopamine transporter

Valérie Fauchey
  • Fonction : Auteur
Mohamed Jaber
Marc Caron
  • Fonction : Auteur
Bertrand Bloch
  • Fonction : Auteur

Résumé

Abstract Mice with a genetic disruption of the dopamine transporter (DAT –/– ) exhibit locomotor hyperactivity and profound alterations in the homeostasis of the nigrostriatal system, e.g. a dramatic increase in the extracellular dopamine level. Here, we investigated the adaptive changes in dopamine D1, D2 and D3 receptor gene expression in the caudate putamen and nucleus accumbens of DAT –/– mice. We used quantitative in situ hybridization and found that the constitutive hyperdopaminergia results in opposite regulations in the gene expression for the dopamine receptors. In DAT –/– mice, we observed increased mRNA levels encoding the D3 receptor (caudate putamen, +60–85%; nucleus accumbens, +40–107%), and decreased mRNA levels for both D1 (caudate putamen, −34%; nucleus accumbens, −45%) and D2 receptors (caudate putamen, −36%; nucleus accumbens, −33%). Furthermore, we assessed the phenotypical organization of the striatal efferent neurons by using double in situ hybridization. Our results show that in DAT +/+ mice, D1 and D2 receptor mRNAs are segregated in two different main populations corresponding to substance P and preproenkephalin A mRNA‐containing neurons, respectively. The phenotype of D1 or D2 mRNA‐containing neurons was unchanged in both the caudate putamen and nucleus accumbens of DAT –/– mice. Interestingly, we found an increased density of preproenkephalin A‐negative neurons that express the D3 receptor mRNA in the nucleus accumbens (core, +35%; shell, +46%) of DAT –/– mice. Our data further support the critical role for the D3 receptor in the regulation of D1–D2 interactions, an action being restricted to neurons coexpressing D1 and D3 receptors in the nucleus accumbens.

Dates et versions

hal-04506352 , version 1 (15-03-2024)

Identifiants

Citer

Valérie Fauchey, Mohamed Jaber, Marc Caron, Bertrand Bloch, Catherine Le Moine. Differential regulation of the dopamine D1, D2 and D3 receptor gene expression and changes in the phenotype of the striatal neurons in mice lacking the dopamine transporter. European Journal of Neuroscience, 2000, 12 (1), pp.19-26. ⟨10.1046/j.1460-9568.2000.00876.x⟩. ⟨hal-04506352⟩
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