RGD Reference Report - The role of the dopamine D1 receptor in social cognition: studies using a novel genetic rat model. - Rat Genome Database

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The role of the dopamine D1 receptor in social cognition: studies using a novel genetic rat model.

Authors: Homberg, Judith R  Olivier, Jocelien D A  VandenBroeke, Marie  Youn, Jiun  Ellenbroek, Arabella K  Karel, Peter  Shan, Ling  van Boxtel, Ruben  Ooms, Sharon  Balemans, Monique  Langedijk, Jacqueline  Muller, Mareike  Vriend, Gert  Cools, Alexander R  Cuppen, Edwin  Ellenbroek, Bart A 
Citation: Homberg JR, etal., Dis Model Mech. 2016 Oct 1;9(10):1147-1158. doi: 10.1242/dmm.024752. Epub 2016 May 19.
RGD ID: 13825241
Pubmed: PMID:27483345   (View Abstract at PubMed)
PMCID: PMC5087833   (View Article at PubMed Central)
DOI: DOI:10.1242/dmm.024752   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Drd1Ratcell surface  IDA MMO:0000686RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Drd1Ratdopamine binding  IMP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Drd1Ratabnormal response to social novelty  IMP compared to wild typeRGD 
Drd1m1HubrRatabnormal response to social novelty  IMP compared to wild typeRGD 
WI- Drd1m1HubrRatabnormal response to social novelty  IMP compared to wild typeRGD 
Drd1Ratabnormal social investigation  IMP compared to wild typeRGD 
Drd1m1HubrRatabnormal social investigation  IMP compared to wild typeRGD 
WI- Drd1m1HubrRatabnormal social investigation  IMP compared to wild typeRGD 
Drd1Ratabnormal vocalization  IMP compared to wild typeRGD 
Drd1m1HubrRatabnormal vocalization  IMP compared to wild typeRGD 
WI- Drd1m1HubrRatabnormal vocalization  IMP compared to wild typeRGD 
Drd1Ratdecreased body weight  IMP compared to wild typeRGD 
Drd1m1HubrRatdecreased body weight  IMP compared to wild typeRGD 
WI- Drd1m1HubrRatdecreased body weight  IMP compared to wild typeRGD 
Drd1Ratdecreased vertical activity  IMP compared to wild typeRGD 
Drd1m1HubrRatdecreased vertical activity  IMP compared to wild typeRGD 
WI- Drd1m1HubrRatdecreased vertical activity  IMP compared to wild typeRGD 
Objects Annotated

Genes (Rattus norvegicus)
Drd1  (dopamine receptor D1)
Drd1m1Hubr  (dopamine receptor D1; ENU induced mutant 1, Hubr)

Strains
WI- Drd1m1Hubr  (NA)


Additional Information