Nur77 gene knockout alters dopamine neuron biochemical activity and dopamine turnover

Authors: Gilbert, FrançoisMorissette, MarcSt-Hilaire, MichelPaquet, BrigitteRouillard, ClaudeDi Paolo, ThérèseLévesque, Daniel
Abstract: Background: Transcription factors of the Nur family (Nurr1, Nur77, and Nor-1) are orphan nuclear receptors closely associated with dopamine neurotransmission in the central nervous system. Nur77 expression is strongly modulated by antipsychotic and ant-parkinsonian drugs in dopaminoceptive brain areas. However, the role of Nur77 in dopamine neuron activity and turnover remains elusive. Methods: We compared various behavioral and biochemical parameters between Nur77 knockout −/− and wild-type +/+ mice in basal and haloperidol-challenged conditions. Results: We report here that Nur77-deficient mice display enhanced spontaneous locomotor activity, greater sensitivity to a small dose of the dopamine D2 receptor agonist quinpirole acting mainly at autoreceptor sites, and higher levels of the dopamine metabolite DOPAC relative to wild-type mice. Dopamine turnover disturbances are also found after acute challenge with haloperidol, a dopamine D2 receptor antagonist. These alterations are associated with increased tyrosine hydroxylase expression and activity, and reduced catechol-O-methyltransferase expression. Conclusion: Taken together, these results are consistent with the involvement of Nur77 in dopamine neuron biochemical activity and dopamine turnover.
Document Type: Article de recherche
Issue Date: 15 September 2006
Open Access Date: 12 February 2018
Document version: AM
This document was published in: Biological psychiatry, Vol. 60 (6), 538-547 (2006)
Society of Biological Psychiatry
Alternative version: 10.1016/j.biopsych.2006.04.023
Collection:Articles publiés dans des revues avec comité de lecture

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