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.
Miller
J C
JC
Millhauser Laboratories of the Department of Psychiatry, New York University School of Medicine, NY 10016.
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