The comparative effects of haloperidol, (-)-sulpiride, and SCH23390 on c-fos and c-jun mRNA expressions, and AP-1 DNA binding activity.
The c-fos and c-jun mRNA expressions were measured by the RNase protection assay method following intraperitoneal injection of haloperidol, (D1 and D2 receptor antagonists), (-)-sulpiride, (D2 receptor antagonist), and SCH23390, (D1 receptor antagonist). Haloperidol and (-)-sulpiride increased their mRNA expressions in a dose-dependent manner, peaking at 30 min after injection followed by a gradual decline. The SCH23390 did not induce expression of either c-fos or c-jun mRNA. A significant decrease of c-fos as well as c-jun mRNA expression was found due to pretreatment with SCH23390 (1 mg/kg i.p.) followed by injection of (-)-sulpiride (20 mg/kg i.p.). The results suggest that the expression of these mRNAs is closely related to the dopamine D2-like antagonism. Administration of haloperidol or (-)-sulpiride increased AP-1 DNA binding activity with similar manner of dose-dependence, whereas their activities were reduced by Fos and Jun antibodies, implying that AP-1 components, transcriptional factors, forming due to Fos and Jun were actually activated by either haloperidol or (-)-sulpiride.
Ozaki
T
T
Department of Neuropsychiatry, Osaka City University Medical School, Japan.
Katsumoto
E
E
Yokotani
N
N
Yamagami
S
S
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D006220:Haloperidol / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis*; D015347:RNA Probes; D012333:RNA, Messenger / Q000096:biosynthesis; D012260:Ribonucleases / Q000378:metabolism; D013469:Sulpiride / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D001552:Benzazepines; D018492:Dopamine Antagonists; D009687:Nuclear Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D015347:RNA Probes; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D013469:Sulpiride; D004247:DNA; D012260:Ribonucleases; D006220:Haloperidol