Enhanced preproenkephalin-B-derived opioid transmission in striatum and subthalamic nucleus converges upon globus pallidus internalis in L-3,4-dihydroxyphenylalanine-induced dyskinesia.
Biological Psychiatry. 2007-04-01; 61(7): 836-844
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1. Biol Psychiatry. 2007 Apr 1;61(7):836-44. Epub 2006 Sep 1.
Enhanced preproenkephalin-B-derived opioid transmission in striatum and
subthalamic nucleus converges upon globus pallidus internalis in
Aubert I(1), Guigoni C, Li Q, Dovero S, Bioulac BH, Gross CE, Crossman AR, Bloch
B, Bezard E.
(1)Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche
(UMR) 5541, Bordeaux Cedex, France.
BACKGROUND: A role for enhanced opioid peptide transmission has been suggested in
the genesis of levodopa-induced dyskinesia. However, basal ganglia nuclei other
than the striatum have not been regarded as potential sources, and the opioid
precursors have never been quantified simultaneously with the levels of opioid
receptors at the peak of dyskinesia severity.
METHODS: The levels of messenger RNA (mRNA) encoding the opioid precursors
preproenkephalin-A and preproenkephalin-B in the striatum and the subthalamic
nucleus and the levels of mu, delta, and kappa opioid receptors were measured
within the basal ganglia of four groups of nonhuman primates killed at the peak
of effect: normal, parkinsonian, parkinsonian chronically-treated with levodopa
without exhibiting dyskinesia, and parkinsonian chronically-treated with levodopa
showing overt dyskinesia.
RESULTS: Dyskinesia are associated with reduction in opioid receptor binding and
specifically of kappa and mu receptor binding in the globus pallidus internalis
(GPi), the main output structure of the basal ganglia. This decrease was
correlated with enhancement of the expression of preproenkephalin-B mRNA but not
that of preproenkephalin-A in the striatum and the subthalamic nucleus.
CONCLUSIONS: Abnormal transmission of preproenkephalin-B-derived opioid coming
from the striatum and the subthalamic nucleus converges upon GPi at the peak of
dose to induce levodopa-induced dyskinesia.
PMID: 16950226 [Indexed for MEDLINE]