Pattern of levodopa-induced striatal changes is different in normal and MPTP-lesioned mice.
While levodopa-induced neurochemical changes have been studied in animal models of Parkinson's disease, very little is known regarding the effects of levodopa administration in normal animals. The present study investigates the effects normal and MPTP-lesioned mice chronically treated with two different doses of levodopa. We assess changes in striatal dopamine (DA) receptor binding, striatal DA receptor mRNA levels and striatal neuropeptide precursor levels (preproenkephalin-A [PPE-A]; preprotachykinin [PPT]; preproenkephalin-B [PPE-B]). The extent of the lesion was measured by striatal DA transporter binding and stereological estimation of the number of tyrosine hydroxylase immunoreactive neurones in the substantia nigra pars compacta (SNc). In non-lesioned animals, chronic levodopa treatment induced an increase in PPE-A mRNA, whereas both D3R binding and PPE-B mRNA levels were dramatically increased in the lesioned animals in a dose dependent manner. The present results show that chronic levodopa administration may induce pathophysiological changes, even in the absence of a lesion of the nigro-striatal pathway, suggesting that the sensitization process involves predominantly the indirect striatofugal pathway in non-lesioned animals, whereas the direct pathway is primarily involved in lesioned animals.
Gross
Christian E
CE
Basal Gang, Laboratoire de Neurophysiologie, Universitè Victor Segalen, Bordeaux Cedex, France.
Ravenscroft
Paula
P
Dovero
Sandra
S
Jaber
Mohamed
M
Bioulac
Bernard
B
Bezard
Erwan
E
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D002908:Chronic Disease; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D050483:Dopamine Plasma Membrane Transport Proteins; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins; D009434:Neural Pathways / Q000187:drug effects / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D020734:Parkinsonian Disorders / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D050637:Receptors, Dopamine D3; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology; D015320:Tachykinins / Q000235:genetics / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis
D000978:Antiparkinson Agents; D050483:Dopamine Plasma Membrane Transport Proteins; C493594:Drd3 protein, mouse; D004745:Enkephalins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D015320:Tachykinins; C044206:preprotachykinin; D007980:Levodopa; C033660:preproenkephalin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase