Time course of striatal DeltaFosB-like immunoreactivity and prodynorphin mRNA levels after discontinuation of chronic dopaminomimetic treatment.
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.
Andersson
M
M
Department of Physiological Sciences, Neurobiology Division, Lund University, Wallenberg Neuroscience Center, BMC A11, Sweden.
Westin
J E
JE
Cenci
M A
MA
D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001545:Benserazide / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D003714:Denervation; D004298:Dopamine / Q000502:physiology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004745:Enkephalins / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006892:Hydroxydopamines / Q000633:toxicity; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007980:Levodopa / Q000494:pharmacology; D017072:Neostriatum / Q000166:cytology / Q000378:metabolism*; D009434:Neural Pathways / Q000378:metabolism / Q000502:physiology; D011498:Protein Precursors / Q000096:biosynthesis*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013563:Sympathectomy, Chemical
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D018765:Dopamine Uptake Inhibitors; D004745:Enkephalins; D004791:Enzyme Inhibitors; D006892:Hydroxydopamines; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D007980:Levodopa; D001545:Benserazide; C033660:preproenkephalin; D003042:Cocaine; D004298:Dopamine