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.
Key Words
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Article info
Publication history
Published online: August 10, 2006
Accepted:
April 26,
2006
Received in revised form:
April 25,
2006
Received:
March 1,
2006
Identification
Copyright
© 2006 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
