title: Electroconvulsive shocks decrease α2-adrenoceptor binding in the Flinders rat model of depression.
abstract: Despite years of drug development, electroconvulsive therapy (ECT) remains the most effective treatment for severe depression. The exact therapeutic mechanism of action of ECT is still unresolved and therefore we tested the hypothesis that the beneficial effect of ECT could in part be the result of increased noradrenergic neurotransmission leading to a decrease in α2-adrenoceptor binding. We have previously shown that both the Flinders sensitive line (FSL) and Flinders resistant line (FRL) rats had altered α2-adrenoceptor binding compared to control Sprague-Dawley (SD) rats. In this study, we treated female FSL, FRL and SD rats with electroconvulsive shock (ECS), an animal model of ECT, or sham stimulation for 10 days before brains were removed and cut into 20µm thick sections. Densities of α2-adrenoceptors were measured by quantitative autoradiography in the hippocampus, thalamic nucleus, hypothalamus, amygdala, frontal cortex, insular cortex, and perirhinal cortex using the α2-adrenoceptor antagonist, [(3)H]RX 821002. ECS decreased the binding of α2-adrenoceptors in cortical regions in the FSL and cortical and amygdaloid regions in the control FRL rats compared to their respective sham treated group. The normal SD controls showed no significant response to ECS treatment. Our data suggest that the therapeutic effect of ECS may be mediated through a decrease of α2-adrenoceptors, probably due to a sustained increase in noradrenaline release. These data confirm the importance of the noradrenergic system and the α2-adrenoceptor in depression and in the mechanism of antidepressant treatments.
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Denmark; Center of Functionally Integrative Neuroscience/MINDlab, Aarhus University, Denmark.
authors.forename: Thea P
authors.initials: TP
authors.lastname: Lillethorup
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Iversen
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Denmark; Center of Functionally Integrative Neuroscience/MINDlab, Aarhus University, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Fontain
authors.affiliation: Center for Psychiatric Research, Aarhus University, Denmark; Centre for Pharmaceutical Excellence, School of Pharmacy (Pharmacology), North-West University, Potchefstroom, South Africa.
authors.forename: Gregers
authors.initials: G
authors.lastname: Wegener
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Denmark; Center of Functionally Integrative Neuroscience/MINDlab, Aarhus University, Denmark; Department of Medicine/Neurology, University of British Columbia, Canada.
authors.forename: Doris J
authors.initials: DJ
authors.lastname: Doudet
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Denmark; Center of Functionally Integrative Neuroscience/MINDlab, Aarhus University, Denmark. Electronic address: annie@pet.auh.dk.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Landau
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000493:pharmacokinetics; D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D001703:Biophysics; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003863:Depression / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D004195:Disease Models, Animal; D004597:Electroshock / Q000379:methods*; D005260:Female; D019329:Idazoxan / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D011485:Protein Binding / Q000187:drug effects / Q000528:radiation effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D014316:Tritium / Q000493:pharmacokinetics
chemical_list: D000317:Adrenergic alpha-Antagonists; D018341:Receptors, Adrenergic, alpha-2; D014316:Tritium; C058525:2-methoxyidazoxan; D019329:Idazoxan
keywords: Autoradiography; Electroconvulsive therapy; Flinders resistant line rats; Flinders sensitive line rats; α(2)-Adrenoceptors