title: ADHD-associated dopamine transporter, latrophilin and neurofibromin share a dopamine-related locomotor signature in Drosophila.
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.
authors.affiliation: Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van der Voet
authors.affiliation: Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Harich
authors.affiliation: Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands.|Department of Psychiatry, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Franke
authors.affiliation: Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Schenck
mesh_terms: D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology; D025542:Neurofibromin 1 / Q000235:genetics / Q000378:metabolism; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D025542:Neurofibromin 1; D018000:Receptors, Peptide; C034800:alpha-latrotoxin receptor; D008774:Methylphenidate; D004298:Dopamine