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DA Uptake Sites, D 1 , and D 2 Receptors, D 2 and Preproenkephalin mRNAs and Fos Immunoreactivity in Rat Striatal Subregions after Partial Dopaminergic Degeneration
Author(s) -
Chritin M.,
Blanchard V.,
RaismanVozari R.,
Feuerstein C.,
Agid Y.,
JavoyAgid F.,
Savasta M.
Publication year - 1996
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1996.tb01545.x
Subject(s) - dopaminergic , substantia nigra , pars compacta , striatum , nigrostriatal pathway , dopamine , medicine , neuroscience , endocrinology , population , biology , oxidopamine , environmental health
Stereotaxic injection of a limited amount of 6‐ hydroxydopamine in the lateral part of the rat substantia nigra induces a partial degeneration of the nigrostriatal dopaminergic system. This animal model in which the destruction of the dopaminergic nigral cell population reaches ‐50% could be considered as a preclinical Parkinson's model. Autoradiography of dopaminergic uptake sites performed with a specific marker ([ 3 H]GBR 12935) allowed the precise determination of dopaminergic denervated and non‐denervated areas in the striatum 1 month after partial lesion of the substantia nigra pars compacta. In both striatal areas, dopaminergic D 1 and D 2 receptor densities and dopaminergic D 2 and preproenkephalin mRNAs levels were measured by autoradiography and in situ hybridization coupled to an image analysis system. Our results show that in the denervated striatal subregion, none of the dopaminergic targets were modified, contrary to the observations made after complete lesion of the nigrostriatal DA system at the same post‐lesion delay. However, striatal Fos activation induced by amphetamine (5 mg/kg i.p., 2 h before killing) revealed that the number of Fos‐positive cells detected in the denervated striatal subregion was lower than that observed in the non‐denervated one. These data argue in favour of the existence of compensatory mechanisms different from the up‐regulation of DA receptor densities, thereby allowing the maintenance of striatal dopaminergic transmission. Such mechanisms could contribute to the delay of the appearance of neurological symptoms (which are reported to be clinically apparent only when depletion of striatal dopamine levels reaches near 80%) in Parkinsonian patients.