| Coadministration of (-)-OSU6162 with l-DOPA normalizes preproenkephalin mRNA expression in the sensorimotor striatum of primates with unilateral 6-OHDA lesions. | |
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MedLine Citation:
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PMID: 11312565 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The substituted phenylpiperidine (-)-OSU6162 is a novel modulator of the dopaminergic systems with low affinity for dopamine D(2) receptors and potent normalizing effects on l-DOPA-induced dyskinesias. We studied the effects of coadministration of (-)-OSU6162 with l-DOPA on the regulation of striatal preproenkephalin (PPE) and prodynorphin (PDyn) mRNA expression in the primate brain by in situ hybridization histochemistry. Common marmoset monkeys sustaining unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway received l-DOPA/carbidopa, l-DOPA/carbidopa plus (-)-OSU6162, or vehicle over 14 days. In vehicle-treated animals, PPE mRNA levels were markedly increased in the sensorimotor territory of the lesioned striatum. By contrast, a rather uniform lesion-induced reduction of PDyn mRNA levels was found in the vehicle group. Subchronic l-DOPA treatment induced a further increase in PPE mRNA expression in a number of sensorimotor and associative subregions of the denervated striatum. Coadministration of (-)-OSU6162 with l-DOPA partially reversed the lesion- and l-DOPA-induced elevation of PPE expression and, by affecting PPE mRNA expression differentially on the intact and lesioned striatum, markedly reduced the side-to-side difference in PPE mRNA expression. The effects on PPE mRNA expression were apparent throughout the rostrocaudal extent of the putamen and the dorsal portions of the caudate nucleus. l-DOPA treatment resulted in an enhancement in PDyn mRNA expression in all functional compartments of the striatum. Coadministration of (-)-OSU6162 had no apparent influence on these l-DOPA-induced changes in PDyn mRNA expression. The present results suggest that (-)-OSU6162 acts primarily by modifying striatal output via the indirect pathway. |
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Authors:
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W Pirker; J Tedroff; H Pontén; L Gunne; P E Andrén; Y L Hurd |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Experimental neurology Volume: 169 ISSN: 0014-4886 ISO Abbreviation: Exp. Neurol. Publication Date: 2001 May |
Date Detail:
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Created Date: 2001-04-23 Completed Date: 2001-06-07 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0370712 Medline TA: Exp Neurol Country: United States |
Other Details:
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Languages: eng Pagination: 122-34 Citation Subset: IM |
Copyright Information:
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Copyright 2001 Academic Press. |
Affiliation:
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Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, S-17176, Sweden. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Autoradiography Callithrix Caudate Nucleus / metabolism Corpus Striatum / drug effects*, metabolism Disease Models, Animal Dopamine Agents / administration & dosage Drug Administration Schedule Drug Therapy, Combination Enkephalins / genetics, metabolism* Female In Situ Hybridization Injections, Subcutaneous Levodopa / administration & dosage* Ligands Male Oxidopamine Parkinson Disease, Secondary / chemically induced, drug therapy*, metabolism Piperidines / administration & dosage* Protein Precursors / genetics, metabolism* Putamen / metabolism RNA, Messenger / metabolism Tritium |
| Chemical | |
Reg. No./Substance:
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0/Dopamine Agents; 0/Enkephalins; 0/Levodopa; 0/Ligands; 0/OSU 6162; 0/Piperidines; 0/Protein Precursors; 0/RNA, Messenger; 10028-17-8/Tritium; 1199-18-4/Oxidopamine; 93443-35-7/preproenkephalin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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