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Pattern of levodopa‐induced striatal changes is different in normal and MPTP‐lesioned mice
Author(s) -
Gross Christian E.,
Ravenscroft Paula,
Dovero Sandra,
Jaber Mohamed,
Bioulac Bernard,
Bezard Erwan
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01600.x
Subject(s) - mptp , substantia nigra , pars compacta , neurochemical , tyrosine hydroxylase , levodopa , dopamine , endocrinology , medicine , striatum , neuropeptide , parkinson's disease , basal ganglia , pharmacology , receptor , central nervous system , disease , dopaminergic
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 D 3 R 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.