Novelty-related behavior of young and adult dopamine transporter knockout rats: Implication for cognitive and emotional phenotypic patterns

Genes Brain Behav. 2018 Apr;17(4):e12463. doi: 10.1111/gbb.12463. Epub 2018 Mar 22.

Abstract

Attention deficit hyperactivity disorder (ADHD) is a neuropsychiatric disorder characterized by a developmentally inappropriate, pervasive and persistent pattern of severe inattention, hyperactivity and impulsivity. Despite onset in early childhood, ADHD may continue into adulthood with substantial impairment in social, academic and occupational functioning. A new animal model of this disorder was developed in rats with genetic deletion of the dopamine transporter (DAT) gene (dopamine transporter knockout rats; DAT-KO rats). We analyzed the behavior of DAT-KO rats for a deeper phenotypical characterization of this model. We first tested rats of the 3 genotypes at different ages (preadolescent, adolescent and adult), in a novelty-seeking test using a black/white box (Experiment 1). After that, we tested adult rats in a novelty-preference test using a 3-chamber apparatus with different shapes (Experiment 2). Experiment 1: as evidenced by analysis of time spent in the novel environment, adult DAT heterozygous (DAT-HET) rats show an increased curiosity-driven exploration compared with wild-type (WT) controls while DAT-KO rats did not recognize novelty. The locomotor activity data show a minimal difference between genotypes at adolescent age while the preadolescent and adult DAT-KO rats have significantly increased activity rate compared with WT and DAT-HET subjects. Experiment 2: in this case, due to more clearly evident spatial differences, time spent in novel environment was not significantly different among genotypes. During first 10 minutes, DAT-KO rats showed a decreased hyperactivity, apparently related to curiosity and attention to the new environments. In conclusion, DAT-KO rats may show some inattention while more novelty-seeking traits appear in DAT-HET rats.

Keywords: ADHD; DAT-HET (heterozygous); adolescence; explorative curiosity; hippocampus; inattention; juvenile; novelty preference; novelty seeking; prefrontal cortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Attention Deficit Disorder with Hyperactivity / genetics
  • Cognition / physiology
  • Disease Models, Animal
  • Dopamine Plasma Membrane Transport Proteins / genetics*
  • Emotions / physiology
  • Exploratory Behavior / physiology*
  • Female
  • Gene Knockout Techniques
  • Impulsive Behavior / physiology
  • Male
  • Motor Activity / genetics
  • Rats
  • Rats, Wistar

Substances

  • Dopamine Plasma Membrane Transport Proteins