title: Reduced striatal D1 receptor binding in autosomal dominant nocturnal frontal lobe epilepsy.
abstract: BACKGROUND
  Mutations of the neuronal nicotinic acetylcholine (nACh) receptor identified in patients with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) lead to increased sensitivity to ACh. As activation of presynaptic nicotinic receptors augments the release of dopamine in the striatum and the prefrontal regions, we tested the hypothesis that that the alpha4-Ser248Phe mutation affects dopaminergic transmission.
  
  
  METHODS
  We measured D(1) receptor binding using [(11)C]-SCH23390 and PET in 12 subjects with the alpha4-Ser248Phe mutation (3 men, mean age 41 +/- 16 years) and 19 controls (8 men, mean age 36 +/- 13 years) matched for gender, smoking status, and age. Parametric images were produced using the simplified reference region method. Both MRI-based regions of interest and voxel based analyses were used.
  
  
  RESULTS
  Reduced striatal [(11)C]-SCH23390 binding occurred with the mutation (controls 1.1 +/- 0.1; ADNFLE 0.97 +/- 0.2; p < 0.01). Statistical parametric mapping confirmed a region of reduced [(11)C]-SCH23390 binding in the right putamen in alpha4-Ser248Phe subjects compared to controls (309 voxels, local maxima 20 16 -2 mm; Z(score) 3.57, p < 0.05).
  
  
  CONCLUSIONS
  Reduced D(1) receptor binding may represent increased extracellular dopamine levels or, more likely, receptor downregulation. Alterations in mesostriatal dopaminergic circuits may contribute to nocturnal paroxysmal motor activity in autosomal dominant nocturnal frontal lobe epilepsy.
authors.affiliation: Department of Medicine, The University of Melbourne, Victoria, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Fedi
authors.forename: S F
authors.initials: SF
authors.lastname: Berkovic
authors.forename: I E
authors.initials: IE
authors.lastname: Scheffer
authors.forename: G
authors.initials: G
authors.lastname: O'Keefe
authors.forename: C
authors.initials: C
authors.lastname: Marini
authors.forename: R
authors.initials: R
authors.lastname: Mulligan
authors.forename: S
authors.initials: S
authors.lastname: Gong
authors.forename: H
authors.initials: H
authors.lastname: Tochon-Danguy
authors.forename: D C
authors.initials: DC
authors.lastname: Reutens
mesh_terms: D000328:Adult; D003342:Corpus Striatum / Q000378:metabolism*; D017034:Epilepsy, Frontal Lobe / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020183:Nocturnal Paroxysmal Dystonia / Q000235:genetics / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding / Q000502:physiology; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D017447:Receptors, Dopamine D1