Acute and repeated treatment with L-DOPA increase c-jun expression in the 6-hydroxydopamine-lesioned forebrain of rats and common marmosets.
L-DOPA was acutely or repeatedly administered to rats and common marmosets (Callithrix jacchus) with unilateral 6-hydroxydopamine (6-OHDA) denervation of the dopamine inputs to the forebrain. Using in situ hybridization it was found that L-DOPA-treated animals exhibited a pronounced induction in the gene expression of both c-jun and c-fos in striatum and cerebral cortex restricted to the dopamine-depleted hemisphere. In contrast, acute treatment with cocaine induced c-fos mRNA, but not c-jun mRNA, in the striatum of normal animals. These data suggest that dopamine denervation leads to neurochemical adaptations which enables L-DOPA to induce a sustained gene expression of c-jun. Such aberrant gene regulation may underlie the development of L-DOPA-induced movement disorders which are commonly found in patients with Parkinson's disease.
Svenningsson
Per
P
Department of Physiology and Pharmacology, Karolinska Institute, SE-171 77, Stockholm, Sweden.
Arts
Joris
J
Gunne
Lars
L
Andren
Per E
PE
D000818:Animals; D002144:Callithrix; D004334:Drug Administration Schedule; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D016762:Genes, fos / Q000187:drug effects / Q000502:physiology; D016758:Genes, jun / Q000187:drug effects* / Q000502:physiology; D007276:Injections, Intraventricular; D007980:Levodopa / Q000008:administration & dosage*; D016627:Oxidopamine / Q000633:toxicity*; D016548:Prosencephalon / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D012333:RNA, Messenger; D007980:Levodopa; D016627:Oxidopamine