Consequences of an intrastriatal injection of kainic acid on the dopaminergic neuronal and vesicular uptake systems.
Intrastriatal kainic acid injection destroys the neurons originating from the striatum, including those on which terminals of the nigro- and meso-striatal dopaminergic neurons project. We have studied at various times the consequences of this lesion on dopamine metabolism and on the neuronal and vesicular transporters. Two and 15 days after kainic acid injection, whereas dopamine turnover was increased and the dopamine content unchanged, there was no modification in the binding of [3H]GBR 12783, a marker of the neuronal uptake complex, but the binding of [3H]dihydrotetrabenazine, a marker of the vesicular transporter, was significantly decreased. At later times (30 and 60 days) when the dopamine turnover was decreased as well as the dopamine content, the binding of [3H]dihydrotetrabenazine was more dramatically decreased (about 30% of controls) than that of [3H]GBR 12783. In addition autoradiography showed an increase in the density of [3H]dihydrotetrabenazine binding sites in the substantia nigra. Thus it appears that the long-term (60 days) repercussions of a kainic acid lesion affect simultaneously the dopamine turnover (which is decreased) and the vesicular transporter whereas the dopamine uptake complex is little affected.
Unité de Neuropsychopharmacologie Expérimentale, U.R.A. 1170, CNRS, Faculté de Médecine et de Pharmacie de Rouen, Saint Etienne du Rouvray France.
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Naudon
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Leroux-Nicollet
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Costentin
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001692:Biological Transport; D002794:Choline / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism*; D015259:Dopamine Agents / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D006719:Homovanillic Acid / Q000378:metabolism; D007608:Kainic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008845:Microinjections; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010879:Piperazines / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D013747:Tetrabenazine / Q000031:analogs & derivatives / Q000378:metabolism; D014316:Tritium
D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010879:Piperazines; D014316:Tritium; D015102:3,4-Dihydroxyphenylacetic Acid; C032811:dihydrotetrabenazine; C039737:1-(2-(diphenylmethoxy)ethyl)-4-(3-phenyl-2-propenyl)piperazine; C001746:3-methoxytyramine; D002794:Choline; D007608:Kainic Acid; D004298:Dopamine; D006719:Homovanillic Acid; D013747:Tetrabenazine