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: M Fedi, S F Berkovic, I E Scheffer, G O'Keefe, C Marini, R Mulligan, S Gong, H Tochon-Danguy, D C Reutens
• Journal: Neurology (Neurology) Vol. 71 Issue 11 Pg. 795-8 (Sep 09 2008) ISSN: 1526-632X [Electronic] United States
• PMID: 18685138 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Receptors, Dopamine D1

Topics

• Adult
• Corpus Striatum (metabolism)
• Epilepsy, Frontal Lobe (genetics, metabolism)
• Female
• Genes, Dominant (genetics)
• Humans
• Male
• Middle Aged
• Nocturnal Paroxysmal Dystonia (genetics, metabolism)
• Positron-Emission Tomography (methods)
• Protein Binding (physiology)
• Receptors, Dopamine D1 (antagonists & inhibitors, metabolism)