Haloperidol regulates neurotensin gene expression in striatum of c-fos-deficient mice.
The immediate-early gene c-fos has been proposed to play a role in induction of neurotensin/neuromedin N (NT/N) gene expression in the striatum following acute haloperidol (HAL) treatment. We utilized mice with targeted disruption of the c-fos gene to directly test this hypothesis. A robust increase in NT/N gene expression was observed in the dorsolateral striatum (DLSt) in both wild-type (WT) and c-fos-deficient mice 4-6 h after a single injection of HAL (1 or 4 mg/kg) indicating that products of the c-fos gene are not absolutely required for induction of NT/N mRNA. The basal expression of preprotachykinin, preproenkephalin and preprocholecystokinin mRNAs did not differ between WT and c-fos knockout mice. HAL treatment first increased striatal NT/N mRNA on postnatal day (PD) 10. HAL-induced NT/N mRNA levels were significantly lower in c-fos knockout mice than in WT mice on PD 10 and 15. These findings indicate that reliance on c-fos may be greater earlier in development and that redundant molecular pathways can lead to induction of NT/N mRNA in mouse striatum.
Shearman
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LP
Massachusetts General Hospital, Department of Pediatrics, Harvard Medical School, Boston 02114, USA.
Weaver
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DR
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology*; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D009496:Neurotensin / Q000187:drug effects* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*
D016760:Proto-Oncogene Proteins c-fos; D009496:Neurotensin; D006220:Haloperidol