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.
journal_name
Biol Psychiatryjournal_title
Biological psychiatryauthors
Gilbert F,Morissette M,St-Hilaire M,Paquet B,Rouillard C,Di Paolo T,Lévesque Ddoi
10.1016/j.biopsych.2006.04.023subject
Has Abstractpub_date
2006-09-15 00:00:00pages
538-47issue
6eissn
0006-3223issn
1873-2402pii
S0006-3223(06)00534-8journal_volume
60pub_type
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