title: Increased GABAA receptor binding in amygdala after prenatal administration of valproic acid to rats.
abstract: OBJECTIVE
  Prenatal exposure to valproic acid (VPA) enhances the risk for later development of autism spectrum disorders (ASD). An altered gamma-aminobutyric acid (GABA) system may be a key factor in ASD. Here we investigated possible changes in the GABA system in rats exposed to a low dose of prenatal VPA.
  
  
  METHODS
  We performed autoradiography with [3H]muscimol, (a GABAA receptor agonist), and [11C]Ro15-4513 (a partial agonist of the GABAA α1+5 receptor subtypes), in brain sections containing amygdala, thalamus and hippocampus of rats treated prenatally with 20 mg/kg VPA or saline from the 12th day of gestation. Result Prenatal VPA significantly increased [11C]Ro15-4513 binding in the left amygdala compared with controls (p<0.05). This difference was not observed in the hippocampus, thalamus or right amygdala. No differences were observed in [3H]muscimol binding.
  
  
  CONCLUSIONS
  We observed an asymmetric increase in GABAA receptor binding. Disturbances in the GABAA receptor system have also been detected in human autism with [11C]Ro15-4513.
authors.affiliation: 1Centre of Functionally Integrative Neuroscience,Aarhus University,Aarhus,Denmark.
authors.forename: Freja
authors.initials: F
authors.lastname: Bertelsen
authors.affiliation: 1Centre of Functionally Integrative Neuroscience,Aarhus University,Aarhus,Denmark.
authors.forename: Arne
authors.initials: A
authors.lastname: Møller
authors.affiliation: 1Centre of Functionally Integrative Neuroscience,Aarhus University,Aarhus,Denmark.
authors.forename: Davide
authors.initials: D
authors.lastname: Folloni
authors.affiliation: 1Centre of Functionally Integrative Neuroscience,Aarhus University,Aarhus,Denmark.
authors.forename: Kim Ryun
authors.initials: KR
authors.lastname: Drasbek
authors.affiliation: 1Centre of Functionally Integrative Neuroscience,Aarhus University,Aarhus,Denmark.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Scheel-Krüger
authors.affiliation: 2Department of Nuclear Medicine and PET Centre,Aarhus University and Hospital,Aarhus,Denmark.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Landau
mesh_terms: D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D000067877:Autism Spectrum Disorder / Q000139:chemically induced* / Q000378:metabolism; D001345:Autoradiography; D001386:Azides / Q000493:pharmacokinetics; D001569:Benzodiazepines / Q000493:pharmacokinetics; D002250:Carbon Radioisotopes; D004195:Disease Models, Animal; D005260:Female; D018682:GABA Agents / Q000008:administration & dosage*; D058785:GABA-A Receptor Agonists / Q000493:pharmacokinetics; D008297:Male; D009118:Muscimol / Q000493:pharmacokinetics; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D014635:Valproic Acid / Q000008:administration & dosage*
chemical_list: D001386:Azides; D002250:Carbon Radioisotopes; D018682:GABA Agents; D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D009118:Muscimol; D014635:Valproic Acid; C042957:Ro 15-4513
keywords: GABA; [11C]Ro-154513; autism spectrum disorders; autoradiography; valproic acid