Time course of striatal DeltaFosB-like immunoreactivity and prodynorphin mRNA levels after discontinuation of chronic dopaminomimetic treatment.
2003 (English)In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 17, no 3, 661-6 p.Article in journal (Refereed) Published
DeltaFosB-like proteins are particularly stable transcription factors that accumulate in the brain in response to chronic perturbations. In this study we have compared the time-course of striatal FosB/DeltaFosB-like immunoreactivity and prodynorphin mRNA expression after discontinuation of chronic cocaine treatment to intact rats and chronic L-DOPA treatment to unilaterally 6-hydroxydopamine (6-OHDA) lesioned rats. The animals were killed between 3 h and 16 days after the last drug injection. In both treatment paradigms, the drug-induced FosB/DeltaFosB immunoreactivity remained significantly elevated in the caudate putamen even at the longest withdrawal period examined. The concomitant upregulation of prodynorphin mRNA, a target of DeltaFosB, paralleled the time-course of DeltaFosB-like immunoreactivity in the 6-OHDA-lesion/L-DOPA model, but was more transient in animals treated with cocaine. These results suggest that DeltaFosB-like proteins have exceptional in vivo stability. In the dopamine-denervated striatum, these proteins may exert sustained effects on the expression of their target genes long after discontinuation of L-DOPA pharmacotherapy.
Place, publisher, year, edition, pages
2003. Vol. 17, no 3, 661-6 p.
IdentifiersURN: urn:nbn:se:uu:diva-149243PubMedID: 12581184OAI: oai:DiVA.org:uu-149243DiVA: diva2:404225