Differential dopaminergic regulation of proenkephalin and prodynorphin mRNAs in the basal ganglia of rats.
Proenkephalin and prodynorphin mRNA levels in the caudate-putamen and in the nucleus accumbens of rats were measured by in situ hybridization 2, 4 and 8 weeks following unilateral lesion of the medial forebrain bundle by 6-hydroxydopamine (6-OHDA). After 2 weeks a 60% increase of the levels of proenkephalin mRNA in the ipsilateral caudate-putamen was observed which declined to 20% above control after 8 weeks. A smaller increase in the levels of proenkephalin mRNA of about 20% was observed in the nucleus accumbens after 2 weeks and no significant alteration could be observed 4 and 8 weeks after lesioning. The levels of prodynorphin mRNA in the ipsilateral caudate-putamen decreased 20% below control and returned to control levels 4 and 8 weeks post-lesion. In contrast, in the nucleus accumbens a persistent ipsilateral decrease of prodynorphin (20-30%) was found 2, 4 and 8 weeks post-lesion. These findings indicate, that lesions of the mesostriatal dopamine (DA) system differentially influences opioidergic gene expression in distinct areas of the caudate-putamen. The lesions cause an increase in proenkephalin mRNA levels which was higher in the caudate-putamen than in the nucleus accumbens and tend to be reversible. Conversely, the lesion caused a persistent decrease in the levels of prodynorphin mRNA in the nucleus accumbens and a small and transient decrease in the caudate-putamen.
Reimer
S
S
Physiologisches Institut der Ludwig-Maximilians-Universität München, F.R.G.
Sirinathsinghji
D J
DJ
Nikolorakis
K E
KE
Höllt
V
V
D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000502:physiology*; D002421:Caudate Nucleus / Q000502:physiology; D015342:DNA Probes; D004298:Dopamine / Q000378:metabolism*; D004745:Enkephalins / Q000096:biosynthesis / Q000235:genetics*; D007839:Functional Laterality; D006892:Hydroxydopamines / Q000494:pharmacology*; D008297:Male; D009693:Nucleic Acid Hybridization; D009714:Nucleus Accumbens / Q000502:physiology; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics*; D011699:Putamen / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D015342:DNA Probes; D004745:Enkephalins; D006892:Hydroxydopamines; D011498:Protein Precursors; D012333:RNA, Messenger; C029992:proenkephalin; C027802:5-hydroxydopamine; C033660:preproenkephalin; D004298:Dopamine