Format

Send to

Choose Destination
Biol Psychiatry. 2006 Sep 15;60(6):538-47. Epub 2006 Aug 7.

Nur77 gene knockout alters dopamine neuron biochemical activity and dopamine turnover.

Author information

1
Neuroscience Unit, CRCHUL and Faculty of Medicine, Laval University, Ste-Foy, Quebec, Canada.

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.

PMID:
16893530
PMCID:
PMC5148625
DOI:
10.1016/j.biopsych.2006.04.023
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center