Haloperidol and fluphenazine induce junB gene expression in rat striatum and nucleus accumbens.
Administration of neuroleptics such as haloperidol to rats is known to induce the expression of the immediate-early genes (IEGs) c-fos and zif/268 in striatal neurones. Another IEG, junB, is of interest because it may be involved in the suppression, rather than the enhancement, of downstream gene transcription. In this study, rat striatal tissue was assayed for IEG expression by in situ hybridisation, after the injection of haloperidol (1 mg/kg) or fluphenazine (3 mg/kg). In addition to c-fos mRNA and zif/268 mRNA, neurones in both the striatum and nucleus accumbens were found to contain high levels of junB mRNA, after treatment with either haloperidol or fluphenazine. The proportion of striatal neurones expressing junB mRNA strongly suggests that induction occurs in striatal projection neurones. A significant increase in the levels of the mRNA encoding another IEG, junD, was also detected after haloperidol treatment. The atypical neuroleptic clozapine (3 mg/kg) did not induce the expression of any of these IEGs in striatal tissue. The results show additional complexity in the pattern of IEG induction after neuroleptic administration and suggest that junB is involved in mediating some of the effects of neuroleptics on striatal gene expression.
Simpson
C S
CS
Department of Pharmacology, University of Glasgow, Scotland, UK.
Morris
B J
BJ
D000818:Animals; D003342:Corpus Striatum / Q000737:chemistry / Q000378:metabolism*; D005476:Fluphenazine / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D017781:Genes, Immediate-Early; D016758:Genes, jun; D006220:Haloperidol / Q000494:pharmacology*; D017403:In Situ Hybridization; D008297:Male; D009474:Neurons / Q000737:chemistry; D009714:Nucleus Accumbens / Q000737:chemistry / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic
D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D006220:Haloperidol; D005476:Fluphenazine