Induction of c-fos mRNA expression in rat striatum by neuroleptic drugs.
The effect of selective dopamine D2 receptor-acting drugs on striatal c-fos mRNA expression in the rat has been investigated by Northern hybridization and autoradiography to determine a possible role for c-fos in the initiation of adaptive changes in D2 receptor number by neuroleptic drugs. The neuroleptic drug haloperidol, a D2 receptor antagonist, was found to produce a rapid and transient induction of c-fos mRNA expression as compared with the expression in animals treated with saline. This induction by haloperidol was found to be dose dependent and D2 receptor mediated, inasmuch as a D2 agonist completely reversed the induction and the inactive isomer of the neuroleptic butaclamol, which does not produce an increase in D2 receptors, had no effect on c-fos mRNA expression. From these data, it can be concluded that c-fos expression in striatum is under dopamine D2 receptor-mediated inhibitory control. It is suggested that c-fos may play a role in the initiation of the increase in D2 receptor number produced by chronic neuroleptic drug treatment.
Millhauser Laboratories of the Department of Psychiatry, New York University School of Medicine, NY 10016.
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JC
Miller
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002069:Butaclamol / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D004268:DNA-Binding Proteins; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D019257:Quinpirole; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D014150:Antipsychotic Agents; D004268:DNA-Binding Proteins; D015259:Dopamine Agents; D004873:Ergolines; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D019257:Quinpirole; D002069:Butaclamol; D006220:Haloperidol