title: The role of the dopamine D1 receptor in social cognition: studies using a novel genetic rat model.
abstract: Social cognition is an endophenotype that is impaired in schizophrenia and several other (comorbid) psychiatric disorders. One of the modulators of social cognition is dopamine, but its role is not clear. The effects of dopamine are mediated through dopamine receptors, including the dopamine D1 receptor (Drd1). Because current Drd1 receptor agonists are not Drd1 selective, pharmacological tools are not sufficient to delineate the role of the Drd1. Here, we describe a novel rat model with a genetic mutation in Drd1 in which we measured basic behavioural phenotypes and social cognition. The I116S mutation was predicted to render the receptor less stable. In line with this computational prediction, this Drd1 mutation led to a decreased transmembrane insertion of Drd1, whereas Drd1 expression, as measured by Drd1 mRNA levels, remained unaffected. Owing to decreased transmembrane Drd1 insertion, the mutant rats displayed normal basic motoric and neurological parameters, as well as locomotor activity and anxiety-like behaviour. However, measures of social cognition like social interaction, scent marking, pup ultrasonic vocalizations and sociability, were strongly reduced in the mutant rats. This profile of the Drd1 mutant rat offers the field of neuroscience a novel genetic rat model to study a series of psychiatric disorders including schizophrenia, autism, depression, bipolar disorder and drug addiction.
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, Radboud University Medical Centre, Nijmegen 6525 EZ, The Netherlands.
authors.forename: Judith R
authors.identifier: 0000-0001-9108-7188
authors.initials: JR
authors.lastname: Homberg
authors.affiliation: Department of Neurobiology, Unit Behavioural Neuroscience, Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen 9700 CC, The Netherlands j.d.a.olivier@rug.nl.
authors.forename: Jocelien D A
authors.identifier: 0000-0003-4654-9763
authors.initials: JD
authors.lastname: Olivier
authors.affiliation: Victoria University of Wellington, School of Psychology, PO Box 600, Wellington 6040, New Zealand.
authors.forename: Marie
authors.initials: M
authors.lastname: VandenBroeke
authors.affiliation: Victoria University of Wellington, School of Psychology, PO Box 600, Wellington 6040, New Zealand.
authors.forename: Jiun
authors.initials: J
authors.lastname: Youn
authors.affiliation: Victoria University of Wellington, School of Psychology, PO Box 600, Wellington 6040, New Zealand.
authors.forename: Arabella K
authors.initials: AK
authors.lastname: Ellenbroek
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, Radboud University Medical Centre, Nijmegen 6525 EZ, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Karel
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, Radboud University Medical Centre, Nijmegen 6525 EZ, The Netherlands.
authors.forename: Ling
authors.initials: L
authors.lastname: Shan
authors.affiliation: Hubrecht Institute, KNAW and University Medical Centre Utrecht, Utrecht 3584 CT, The Netherlands.
authors.forename: Ruben
authors.initials: R
authors.lastname: van Boxtel
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, Radboud University Medical Centre, Nijmegen 6525 EZ, The Netherlands.
authors.forename: Sharon
authors.initials: S
authors.lastname: Ooms
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, Radboud University Medical Centre, Nijmegen 6525 EZ, The Netherlands.
authors.forename: Monique
authors.initials: M
authors.lastname: Balemans
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, Radboud University Medical Centre, Nijmegen 6525 EZ, The Netherlands.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Langedijk
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, Radboud University Medical Centre, Nijmegen 6525 EZ, The Netherlands.
authors.forename: Mareike
authors.initials: M
authors.lastname: Muller
authors.affiliation: CMBI, Radboud University Nijmegen Medical Centre, Geert Grooteplein 26-28, Nijmegen 6525 GA, The Netherlands.
authors.forename: Gert
authors.initials: G
authors.lastname: Vriend
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, Radboud University Medical Centre, Nijmegen 6525 EZ, The Netherlands.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Cools
authors.affiliation: Hubrecht Institute, KNAW and University Medical Centre Utrecht, Utrecht 3584 CT, The Netherlands.
authors.forename: Edwin
authors.initials: E
authors.lastname: Cuppen
authors.affiliation: Victoria University of Wellington, School of Psychology, PO Box 600, Wellington 6040, New Zealand.
authors.forename: Bart A
authors.initials: BA
authors.lastname: Ellenbroek
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003071:Cognition; D004195:Disease Models, Animal; D005106:Exploratory Behavior; D006120:Grooming; D008024:Ligands; D008297:Male; D018782:Maze Learning; D008957:Models, Genetic; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000737:chemistry / Q000235:genetics*; D012919:Social Behavior; D014465:Ultrasonics; D014828:Vocalization, Animal
chemical_list: D008024:Ligands; D017447:Receptors, Dopamine D1
keywords: Characterization; Dopamine D1 receptor; Mutant rat; Schizophrenia; Social cognition