The NMDA receptor antagonist MK-801 markedly reduces the induction of c-fos gene by haloperidol in the mouse striatum.
The influence of the N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 (dizocilpine), on the haloperidol-induced increase of c-fos mRNA levels in the striata of mice was examined using the quantitative Northern blot analysis method. Administration of haloperidol (1 mg/kg. i.p.) increased striatal c-fos mRNA hybridization signal about 7-fold, as measured 30 min after injection. MK-801 (0.2-4.5 mg/kg, i.p.) dose-dependently reduced this effect of the dopamine antagonist. Higher doses of MK-801 (1.5-4.5 mg/kg) diminished c-fos mRNA increase produced by haloperidol by 80%. Such a marked inhibition of this haloperidol effect by MK-801 has not been previously reported. It suggests that the induction of c-fos gene occurring in the striatum after dopamine D2 receptor blockade is mediated in great part by endogenous glutamate acting at NMDA receptors. Since the c-fos gene protein product (Fos) is a transcription factor, our results also indicate the involvement of glutamate in the regulation of expression of other genes in the striatum.
Ziólkowska
B
B
Physiologisches Institut, Universität München, FRG.
Höllt
V
V
D000818:Animals; D015152:Blotting, Northern; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos; D006220:Haloperidol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D017403:In Situ Hybridization; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D015347:RNA Probes; D012333:RNA, Messenger / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D016760:Proto-Oncogene Proteins c-fos; D015347:RNA Probes; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D006220:Haloperidol