ADHD-associated dopamine transporter, latrophilin and neurofibromin share a dopamine-related locomotor signature in Drosophila

Mol Psychiatry. 2016 Apr;21(4):565-73. doi: 10.1038/mp.2015.55. Epub 2015 May 12.

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neuropsychiatric disorder with hyperactivity as one of the hallmarks. Aberrant dopamine signaling is thought to be a major theme in ADHD, but how this relates to the vast majority of ADHD candidate genes is illusive. Here we report a Drosophila dopamine-related locomotor endophenotype that is shared by pan-neuronal knockdown of orthologs of the ADHD-associated genes Dopamine transporter (DAT1) and Latrophilin (LPHN3), and of a gene causing a monogenic disorder with frequent ADHD comorbidity: Neurofibromin (NF1). The locomotor signature was not found in control models and could be ameliorated by methylphenidate, validating its relevance to symptoms of the disorder. The Drosophila ADHD endophenotype can be further exploited in high throughput to characterize the growing number of candidate genes. It represents an equally useful outcome measure for testing chemical compounds to define novel treatment options.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Attention Deficit Disorder with Hyperactivity / metabolism*
  • Disease Models, Animal
  • Dopamine / metabolism
  • Dopamine Plasma Membrane Transport Proteins / genetics
  • Dopamine Plasma Membrane Transport Proteins / metabolism*
  • Drosophila
  • Male
  • Methylphenidate / pharmacology
  • Neurofibromin 1 / genetics
  • Neurofibromin 1 / metabolism
  • Receptors, Peptide / genetics
  • Receptors, Peptide / metabolism
  • Signal Transduction

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • Neurofibromin 1
  • Receptors, Peptide
  • alpha-latrotoxin receptor
  • Methylphenidate
  • Dopamine