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.
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. Dopamineturnover 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.
Authors: J A Gogos; M Morgan; V Luine; M Santha; S Ogawa; D Pfaff; M Karayiorgou Journal: Proc Natl Acad Sci U S A Date: 1998-08-18 Impact factor: 11.205
Authors: Isabelle Ethier; Geneviève Beaudry; Michel St-Hilaire; Jeff Milbrandt; Claude Rouillard; Daniel Lévesque Journal: Neuropsychopharmacology Date: 2004-02 Impact factor: 7.853
Authors: Jérôme Maheux; Laura Vuillier; Mylène Mahfouz; Claude Rouillard; Daniel Lévesque Journal: Int J Neuropsychopharmacol Date: 2011-04-28 Impact factor: 5.176
Authors: Matthew P Mount; Yi Zhang; Mandana Amini; Steve Callaghan; Jerzy Kulczycki; Zixu Mao; Ruth S Slack; Hymie Anisman; David S Park Journal: J Biol Chem Date: 2013-03-27 Impact factor: 5.157
Authors: Iftach Shaked; Richard N Hanna; Helena Shaked; Grzegorz Chodaczek; Heba N Nowyhed; George Tweet; Robert Tacke; Alp Bugra Basat; Zbigniew Mikulski; Susan Togher; Jacqueline Miller; Amy Blatchley; Shahram Salek-Ardakani; Martin Darvas; Minna U Kaikkonen; Graham D Thomas; Sonia Lai-Wing-Sun; Ayman Rezk; Amit Bar-Or; Christopher K Glass; Hozefa Bandukwala; Catherine C Hedrick Journal: Nat Immunol Date: 2015-11-02 Impact factor: 25.606