| First Author | Ethier I | Year | 2004 |
| Journal | Neuropsychopharmacology | Volume | 29 |
| Issue | 2 | Pages | 335-46 |
| PubMed ID | 14603264 | Mgi Jnum | J:106200 |
| Mgi Id | MGI:3617732 | Doi | 10.1038/sj.npp.1300318 |
| Citation | Ethier I, et al. (2004) The transcription factor NGFI-B (Nur77) and retinoids play a critical role in acute neuroleptic-induced extrapyramidal effect and striatal neuropeptide gene expression. Neuropsychopharmacology 29(2):335-46 |
| abstractText | Despite extensive investigation, the cellular mechanisms responsible for neuroleptic actions remain elusive. We have previously shown that neuroleptics modulated the expression of some members of the ligand-activated transcription factors (nuclear receptors) including the nerve-growth factor inducible gene B (NGFI-B or Nur77) and retinoid X receptor (RXR) isoforms. Using genetic and pharmacological approaches, we investigated the role of NGFI-B and retinoids in acute behavioral and biochemical responses to dopamine antagonists. NGFI-B knockout (KO) mice display a profound alteration of haloperidol-induced catalepsy and striatal neuropeptide gene expression. Haloperidol-induced increase of striatal enkephalin mRNA is totally abolished in NGFI-B KO mice whereas the increase of neurotensin mRNA expression is reduced by 50%. Interestingly, catalepsy induced by raclopride, a specific dopamine D(2)/D(3) antagonist is completely abolished in NGFI-B-deficient mice whereas the cataleptic response to SCH 23390, a dopamine D(1) agonist, is preserved. Accordingly, the effects of haloperidol on striatal c-fos, Nor-1, and dynorphin mRNA expression are also preserved in NGFI-B-deficient mice. The cataleptic response and the increase of enkephalin mRNA expression induced by haloperidol can also be suppressed by administration of retinoid ligands 9-cis retinoic acid and docosahexaenoic acid. In addition, we demonstrate that haloperidol enhances colocalization of NGFI-B and RXRgamma1 isoform mRNAs, suggesting that both NGFI-B and a RXR isoform are highly coexpressed after haloperidol administration. Our data demonstrate, for the first time, that NGFI-B and retinoids are actively involved in the molecular cascade induced by neuroleptic drugs. |
