Altered D(1) dopamine receptor trafficking in parkinsonian and dyskinetic non-human primates.
Neurobiology of Disease. 2007-05-01; 26(2): 452-463
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1. Neurobiol Dis. 2007 May;26(2):452-63. Epub 2007 Feb 9.
Altered D(1) dopamine receptor trafficking in parkinsonian and dyskinetic
Guigoni C(1), Doudnikoff E, Li Q, Bloch B, Bezard E.
(1)CNRS UMR 5227, Université Victor Segalen-Bordeaux 2, 146 rue Léo Saignat,
33076 Bordeaux, France.
Dyskinesias represent a debilitating complication of levodopa therapy for
Parkinson’s disease (PD). While we recently demonstrated that levodopa-induced
dyskinesia results from increased dopamine D(1) receptor-mediated transmission,
we also questioned the possible role of subcellular localization of D(1) and D(2)
receptors in mediating these effects as we previously showed that D(1) receptors
undergo differential trafficking in striatal neurons of non-dyskinetic PD
patients. Taking advantage of a monkey brain bank, we here report changes
affecting the cellular and subcellular distribution of D(1) and D(2) dopamine
receptors within the striatum of three experimental groups: normal, parkinsonian
and dyskinetic L-dopa-treated parkinsonian animals. Our studies at both light and
electron microscopy levels show a recruitment of D(1) receptor at the plasma
membrane of striatal neurons in the parkinsonian animals and a strong increase of
D(1) expression both at the membrane and in cytoplasm of dyskinetic animals,
whereas D(2) receptor distribution is only modestly affected in all conditions.
Our results rule out the hypothesis of a pathological overinternalization of
dopamine receptors in levodopa-induced dyskinesia but raise the possibility for
involvement of D(1) receptors in the priming phenomenon through massive and
sudden internalization in response to the first ever administration of L-dopa and
for an altered homologous desensitization mechanism in dyskinesia leading to an
increased availability of D(1) receptors at membrane. Further experiments
including parkinsonian monkeys chronically treated with L-dopa that show no
dyskinesia and parkinsonian monkeys treated only once with L-dopa are now
necessary to confirm our hypothesis.
PMID: 17350277 [Indexed for MEDLINE]