title: Enhanced preproenkephalin-B-derived opioid transmission in striatum and subthalamic nucleus converges upon globus pallidus internalis in L-3,4-dihydroxyphenylalanine-induced dyskinesia.
abstract: 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.
authors.affiliation: Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 5541, Bordeaux Cedex, France.
authors.forename: Incarnation
authors.initials: I
authors.lastname: Aubert
authors.forename: Céline
authors.initials: C
authors.lastname: Guigoni
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.forename: Sandra
authors.initials: S
authors.lastname: Dovero
authors.forename: Bernard H
authors.initials: BH
authors.lastname: Bioulac
authors.forename: Christian E
authors.initials: CE
authors.lastname: Gross
authors.forename: Alan R
authors.initials: AR
authors.lastname: Crossman
authors.forename: Bertrand
authors.initials: B
authors.lastname: Bloch
authors.forename: Erwan
authors.initials: E
authors.lastname: Bezard
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects; D003342:Corpus Striatum / Q000378:metabolism*; D004347:Drug Interactions; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D017403:In Situ Hybridization / Q000379:methods; D007980:Levodopa / Q000008:administration & dosage / Q000009:adverse effects; D008252:Macaca fascicularis; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011869:Radioligand Assay / Q000379:methods; D011957:Receptors, Opioid / Q000378:metabolism*; D012044:Regression Analysis; D020531:Subthalamic Nucleus / Q000378:metabolism*
chemical_list: D000978:Antiparkinson Agents; D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; D011957:Receptors, Opioid; D007980:Levodopa; C033660:preproenkephalin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine