title: 5-HT(2A) and mGlu2 receptor binding levels are related to differences in impulsive behavior in the Roman Low- (RLA) and High- (RHA) avoidance rat strains.
abstract: The Roman Low- and High-Avoidance rat strains (RLA-I vs RHA-I) have been bidirectionally selected and bred according to their performance in the two-way active avoidance response in the shuttle-box test. Numerous studies have reported a pronounced divergence in emotionality between the two rat strains including differences in novelty seeking, anxiety, stress coping, and susceptibility to addictive substances. However, the underlying molecular mechanisms behind these divergent phenotypes are not known. Here, we determined impulsivity using the 5-choice serial reaction time task and levels of serotonin transporter (SERT), 5-HT(2A) and 5-HT(1A) receptor binding using highly specific radioligands ((3)H-escitalopram, (3)H-MDL100907 and (3)H-WAY100635) and mGlu2/3 receptor binding ((3)H-LY341495) using receptor autoradiography in fronto-cortical sections from RLA-I (n=8) and RHA-I (n=8) male rats. In the more impulsive RHA-I rats, 5-HT(2A), 5-HT(1A) and SERT binding in the frontal cortex was significantly higher compared to RLA-I rats. In contrast, mGlu2/3 receptor binding was decreased by 40% in RHA-I rats compared to RLA-I rats. To differentiate between mGlu2 and mGlu3 receptor protein levels, these were further studied using western blotting, which showed non-detectable levels of mGlu2 receptor protein in RHA rats, while no differences were observed for mGlu3 receptor protein levels. Collectively, these data show general congenital differences in the serotonergic system and a pronounced difference in mGlu2 receptor protein levels. We suggest that the differences in the serotonergic system may mediate some of the phenotypic characteristics in this strain such as hyper-impulsivity and susceptibility to drug addiction.
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
authors.forename: A B
authors.initials: AB
authors.lastname: Klein
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Ultved
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
authors.forename: D
authors.initials: D
authors.lastname: Adamsen
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
authors.forename: M A
authors.initials: MA
authors.lastname: Santini
authors.affiliation: Departamento de Psiquiatría y Medicina Legal, Instituto de Neurociencias, Universidad Autónoma de Barcelona, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Tobeña
authors.affiliation: Departamento de Psiquiatría y Medicina Legal, Instituto de Neurociencias, Universidad Autónoma de Barcelona, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Fernandez-Teruel
authors.affiliation: Departmento de Neurociencias y Ciencias de la Salud, Universidad de Almería, Almería, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Flores
authors.affiliation: Departmento de Neurociencias y Ciencias de la Salud, Universidad de Almería, Almería, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Moreno
authors.affiliation: Departmento de Neurociencias y Ciencias de la Salud, Universidad de Almería, Almería, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Cardona
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
authors.forename: G M
authors.initials: GM
authors.lastname: Knudsen
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Aznar
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark. Electronic address: jdm@nru.dk.
authors.forename: J D
authors.initials: JD
authors.lastname: Mikkelsen
mesh_terms: D000818:Animals; D001345:Autoradiography; D005625:Frontal Lobe / Q000378:metabolism*; D007175:Impulsive Behavior / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D018094:Receptors, Metabotropic Glutamate; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D044282:Receptor, Serotonin, 5-HT1A
keywords: 5-CSRT; 5-HT(2A); Roman Low- and High-Avoidance rats; impulsivity; mGluR2; receptor binding