Time course of striatal DeltaFosB-like immunoreactivity and prodynorphin mRNA levels after discontinuation of chronic dopaminomimetic treatment

Eur J Neurosci. 2003 Feb;17(3):661-6. doi: 10.1046/j.1460-9568.2003.02469.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aromatic Amino Acid Decarboxylase Inhibitors
  • Benserazide / pharmacology
  • Cocaine / pharmacology
  • Denervation
  • Dopamine / physiology*
  • Dopamine Uptake Inhibitors / pharmacology
  • Enkephalins / biosynthesis*
  • Enzyme Inhibitors / pharmacology
  • Female
  • Hydroxydopamines / toxicity
  • Immunohistochemistry
  • In Situ Hybridization
  • Levodopa / pharmacology
  • Neostriatum / cytology
  • Neostriatum / metabolism*
  • Neural Pathways / metabolism
  • Neural Pathways / physiology
  • Protein Precursors / biosynthesis*
  • Proto-Oncogene Proteins c-fos / metabolism*
  • RNA, Messenger / biosynthesis*
  • Rats
  • Rats, Sprague-Dawley
  • Sympathectomy, Chemical

Substances

  • Aromatic Amino Acid Decarboxylase Inhibitors
  • Dopamine Uptake Inhibitors
  • Enkephalins
  • Enzyme Inhibitors
  • Hydroxydopamines
  • Protein Precursors
  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • Levodopa
  • Benserazide
  • preproenkephalin
  • Cocaine
  • Dopamine