title: Decreased in vivo α2 adrenoceptor binding in the Flinders Sensitive Line rat model of depression.
abstract: Depression is a debilitating heterogeneous disorder and the underlying mechanisms remain elusive. Alterations in monoaminergic neurotransmission, including noradrenergic, have been implicated in the etiology of depression. Although depression is difficult to model in animals, the availability of animal models with face, predictive and construct validity permits more in-depth investigations resulting in a greater understanding of the disease. We investigated the role of noradrenaline (NA) and α2 adrenoceptors in vivo in a genetic model of depression, the Flinders Sensitive Line (FSL) rat. We determined baseline differences in NA receptor volume of distribution to α2 adrenoceptors in FSL, in comparison with two routinely used controls, Flinders Resistant Line (FRL) and Sprague-Dawley (SD) rats using positron emission tomography (PET) imaging and the carbon-11 labeled radioligand yohimbine. We demonstrate a 42-47% reduction in the binding of the tracer in the cortex, striatum, cerebellum, thalamus and pons of FSL rats compared to the two control groups. Our results suggest that the behavioral deficits expressed in the FSL depression model are associated with functional over-activity of the NA system.
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Nørrebrogade 44, Building 10G, Aarhus, 8000, Denmark; Center of Functionally Integrative Neuroscience/MINDlab, Aarhus University, Nørrebrogade 44, Building 10G, Aarhus, 8000, Denmark. Electronic address: annie@pet.auh.dk.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Landau
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Nørrebrogade 44, Building 10G, Aarhus, 8000, Denmark; Department of Biomedicine, Aarhus University, Wilhelm Meyers Allé 4, Aarhus 8000, Denmark. Electronic address: jap@biomed.au.dk.
authors.forename: Jenny-Ann
authors.initials: JA
authors.lastname: Phan
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Nørrebrogade 44, Building 10G, Aarhus, 8000, Denmark. Electronic address: peteiver@rm.dk.
authors.forename: Peter
authors.initials: P
authors.lastname: Iversen
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Nørrebrogade 44, Building 10G, Aarhus, 8000, Denmark; Center of Functionally Integrative Neuroscience/MINDlab, Aarhus University, Nørrebrogade 44, Building 10G, Aarhus, 8000, Denmark. Electronic address: thealillethorup@clin.au.dk.
authors.forename: Thea P
authors.initials: TP
authors.lastname: Lillethorup
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Nørrebrogade 44, Building 10G, Aarhus, 8000, Denmark. Electronic address: simonsen@pet.auh.dk.
authors.forename: Mette
authors.initials: M
authors.lastname: Simonsen
authors.affiliation: Translational Neuropsychiatry Unit, Aarhus University, Skovagervej 2, Building 14J.1, Risskov, 8240, Denmark; Centre for Pharmaceutical Excellence, School of Pharmacy (Pharmacology), North-West University, Privaatsak X6001, Potchefstroom, 2520, South Africa. Electronic address: wegener@clin.au.dk.
authors.forename: Gregers
authors.initials: G
authors.lastname: Wegener
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Nørrebrogade 44, Building 10G, Aarhus, 8000, Denmark. Electronic address: steejako@rm.dk.
authors.forename: Steen
authors.initials: S
authors.lastname: Jakobsen
authors.affiliation: Department of Nuclear Medicine and PET Center, Aarhus University Hospital, Nørrebrogade 44, Building 10G, Aarhus, 8000, Denmark; Department of Medicine/Neurology, University of British Columbia, 2221 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada. Electronic address: ddoudet@mail.ubc.ca.
authors.forename: Doris J
authors.initials: DJ
authors.lastname: Doudet
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003866:Depressive Disorder / Q000000981:diagnostic imaging / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D015016:Yohimbine / Q000493:pharmacokinetics
chemical_list: D002250:Carbon Radioisotopes; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine
keywords: Depression; Flinders sensitive line; Noradrenaline; Positron emission tomography; Yohimbine