Decreased binding capacity (Bmax) of muscarinic acetylcholine receptors in fibroblasts from boys with attention-deficit/hyperactivity disorder (ADHD)

Atten Defic Hyperact Disord. 2013 Sep;5(3):267-71. doi: 10.1007/s12402-013-0103-0. Epub 2013 Feb 7.

Abstract

Monoaminergic dysregulation is implicated in attention-deficit/hyperactivity disorder (ADHD), and methylphenidate and amphetamines are the most frequently prescribed pharmacological agents for treating ADHD. However, it has recently been proposed that the core symptoms of the disorder might be due to an imbalance between monoaminergic and cholinergic systems. In this study, we used fibroblast cell homogenates from boys with and without ADHD as an extraneural cell model to examine the cholinergic receptor density, that is, muscarinic acetylcholine receptors (mAChRs). We found that the binding capacity (Bmax) of [³H] Quinuclidinyl benzilate (³H-QNB) to mAChRs was decreased by almost 50 % in the children with ADHD (mean = 30.6 fmol/mg protein, SD = 25.6) in comparison with controls [mean = 63.1 fmol/mg protein, SD = 20.5, p ≤ 0.01 (Student's unpaired t test)]. The decreased Bmax indicates a reduced cholinergic receptor density, which might constitute a biomarker for ADHD. However, these preliminary findings need to be replicated in larger ADHD and comparison cohorts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Attention Deficit Disorder with Hyperactivity / metabolism*
  • Case-Control Studies
  • Cells, Cultured
  • Child
  • Fibroblasts / metabolism*
  • Humans
  • Male
  • Muscarinic Antagonists / analysis
  • Muscarinic Antagonists / metabolism
  • Quinuclidinyl Benzilate / analysis
  • Quinuclidinyl Benzilate / metabolism
  • Radioligand Assay
  • Receptors, Muscarinic / metabolism*
  • Tritium

Substances

  • Muscarinic Antagonists
  • Receptors, Muscarinic
  • Tritium
  • Quinuclidinyl Benzilate