Effect of repeated administration of dopamine agonists on striatal neuropeptide mRNA expression in rats with a unilateral nigral 6-hydroxydopamine lesion.
Striatal mRNA expression for preproenkephalin (PPE) and preprotachykinin (PPT) was studied in unilateral 6-OHDA lesioned rats treated subchronically with a range of selective and non-selective D-1 or D-2 dopamine (DA) agonists. Apomorphine (5 mg/kg sc), pergolide (0.5 mg/kg sc), SKF 38393 (5 mg/kg sc), SKF 80723 (1.5 mg/kg sc), and quinpirole (5 mg/kg sc), or 0.9% saline (150 microliters sc) were all given twice daily (except pergolide: once daily) for 7 days. The abundance of PPE mRNA was not altered by any of these DA agonists in the intact striatum contralateral to the 6-OHDA lesion. Only apomorphine and quinpirole increased the abundance of PPT mRNA in the intact striatum. In saline treated 6-OHDA lesioned animals PPE mRNA was elevated (+160%, p < 0.005) and PPT mRNA decreased (-36%, p < 0.005) in the denervated striatum. The up-regulation of striatal PPE mRNA in the lesioned striatum was reversed only by pergolide. The downregulation of striatal PPT mRNA in the lesioned striatum was reversed only by apomorphine. The differential sensitivity of the striatal PPE message to the long-acting DA agonist pergolide, and of the striatal PPT message to the mixed D-1/D-2 DA agonist apomorphine suggests that the striatopallidal enkephalinergic pathways are mainly regulated by prolonged DA receptor stimulation, whereas the striatonigral substance P pathways are mainly regulated by mixed D-1/D-2 DA receptor stimulation.
Granata
R
R
Neurodegenerative Disease Research Centre, Biomedical Sciences Division King's College, London, United Kingdom.
Wenning
G K
GK
Jolkkonen
J
J
Jenner
P
P
Marsden
C D
CD
D000818:Animals; D018491:Dopamine Agonists / Q000494:pharmacology*; D004745:Enkephalins / Q000096:biosynthesis; D017403:In Situ Hybridization; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000096:biosynthesis*; D015345:Oligonucleotide Probes; D016627:Oxidopamine; D011498:Protein Precursors / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000819:agonists; D017448:Receptors, Dopamine D2 / Q000819:agonists; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D013563:Sympathectomy, Chemical; D013565:Sympatholytics; D015320:Tachykinins / Q000096:biosynthesis
D018491:Dopamine Agonists; D004745:Enkephalins; D009479:Neuropeptides; D015345:Oligonucleotide Probes; D011498:Protein Precursors; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013565:Sympatholytics; D015320:Tachykinins; C044206:preprotachykinin; D016627:Oxidopamine; C033660:preproenkephalin