title: Neonatal domoic acid alters in vivo binding of [11C]yohimbine to α2-adrenoceptors in adult rat brain.
abstract: Epilepsy is a debilitating seizure disorder that affects approximately 50 million people. Noradrenaline reduces neuronal excitability, has anticonvulsant effects and is protective against seizure onset.
  
  
  
  We investigated the role of α2-adrenoceptors in vivo in a neonatal domoic acid (DOM) rat model of epilepsy.
  
  
  
  We injected male Sprague-Dawley rats daily from postnatal day 8-14 with saline or one of two sub-convulsive doses, 20 μg/kg (DOM20) or 60 μg/kg (DOM60) DOM, an AMPA/kainate receptor agonist. The rats were observed in open field, social interaction and forced swim tests at day 50, 75 and 98, respectively. At ~120 days of age, four rats per group were injected and scanned with [11C]yohimbine, an α2-adrenoceptor antagonist, and scanned in a Mediso micro positron emission tomography (PET) scanner to measure α2-adrenoceptor binding.
  
  
  
  DOM60-treated rats spent more time in the periphery during the open field test and had a significant 26-33 % reduction in [11C]yohimbine binding in the hypothalamus, hippocampus and orbital prefrontal cortex compared to saline-treated rats. On the other hand, DOM20 rats had a significant 34-40 % increase in [11C]yohimbine binding in the hypothalamus, amygdala and entorhinal cortex compared to saline-treated rats, with no obvious behavioural differences.
  
  
  
  The current data clearly indicate that low concentrations of DOM given to rats in their second week of life induces long-term changes in α2-adrenoceptor binding in rat brain that may have relevance to the progression of an epilepsy phenotype.
authors: Department of Nuclear Medicine and PET Center, Aarhus University and Hospital, Aarhus, Denmark.
authors: Majken B
authors: MB
authors: Thomsen
authors: Department of Nuclear Medicine and PET Center, Aarhus University and Hospital, Aarhus, Denmark.
authors: Thea P
authors: TP
authors: Lillethorup
authors: Department of Nuclear Medicine and PET Center, Aarhus University and Hospital, Aarhus, Denmark.
authors: Steen
authors: S
authors: Jakobsen
authors: Department of Nuclear Medicine and PET Center, Aarhus University and Hospital, Aarhus, Denmark.
authors: Erik H
authors: EH
authors: Nielsen
authors: Department of Nuclear Medicine and PET Center, Aarhus University and Hospital, Aarhus, Denmark.
authors: Mette
authors: M
authors: Simonsen
authors: Translational Neuropsychiatry Unit, Aarhus University, Risskov, Denmark.
authors: Gregers
authors: G
authors: Wegener
authors: Department of Nuclear Medicine and PET Center, Aarhus University and Hospital, Aarhus, Denmark. alandau@clin.au.dk.|Translational Neuropsychiatry Unit, Aarhus University, Risskov, Denmark. alandau@clin.au.dk.
authors: Anne M
authors: AM
authors: Landau
authors: Translational Neuropsychiatry Unit, Aarhus University, Risskov, Denmark.|Department of Biomedical Sciences, University of PEI, Charlottetown, Canada.
authors: R Andrew
authors: RA
authors: Tasker
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002250:Carbon Radioisotopes; D004827:Epilepsy / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000378:metabolism; D015016:Yohimbine
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D002250:Carbon Radioisotopes; D009467:Neuromuscular Depolarizing Agents; D019275:Radiopharmaceuticals; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; C012301:domoic acid; D007608:Kainic Acid
keywords: Domoic acid; Epilepsy; Noradrenaline; Positron emission tomography; Yohimbine