Differential expression of inducible transcription factors in basal ganglia neurons.
The dopamine receptor antagonist, haloperidol, produced a time-dependent differential induction of inducible transcription factors (ITFs) in rat striatal neurons: Fos, Fos B, Jun B, Jun D, Krox 20, and Krox 24, but not c-Jun, were induced in the caudate putamen and nucleus accumbens with varying time courses. The induction of Fos by haloperidol was stronger in anterior versus posterior regions of the striatum. In contrast, induction of Fos by the muscarinic agonist pilocarpine was stronger in the posterior regions of the striatum suggesting that muscarinic receptors do not play a role in the induction of ITFs in striatal neurons by haloperidol. Although c-Jun was not induced in caudate neurons by haloperidol it was strongly induced in these neurons following prolonged seizure activity. The differential pattern of Jun protein expression suggests that haloperidol induces a specific transcriptional program in basal ganglia neurons. These effects of haloperidol may be involved in producing its extrapyramidal side effects.
MacGibbon
G A
GA
Department of Pharmacology, University of Auckland, New Zealand.
Lawlor
P A
PA
Hughes
P
P
Young
D
D
Dragunow
M
M
D000818:Animals; D001479:Basal Ganglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010862:Pilocarpine / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000502:physiology; D013226:Status Epilepticus / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis*
D018492:Dopamine Antagonists; D018721:Muscarinic Agonists; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011976:Receptors, Muscarinic; D014157:Transcription Factors; D010862:Pilocarpine; D006220:Haloperidol