Neurochemical and behavioral characterization of neuronal glutamate transporter EAAT3 heterozygous mice

Biol Res. 2017 Sep 19;50(1):29. doi: 10.1186/s40659-017-0138-3.

Abstract

Background: Obsessive-compulsive disorder (OCD) is a severe neuropsychiatric condition affecting 1-3% of the worldwide population. OCD has a strong genetic component, and the SLC1A1 gene that encodes neuronal glutamate transporter EAAT3 is a strong candidate for this disorder. To evaluate the impact of reduced EAAT3 expression in vivo, we studied male EAAT3 heterozygous and wild-type littermate mice using a battery of behavioral paradigms relevant to anxiety (open field test, elevated plus maze) and compulsivity (marble burying), as well as locomotor activity induced by amphetamine. Using high-performance liquid chromatography, we also determined tissue neurotransmitter levels in cortex, striatum and thalamus-brain areas that are relevant to OCD.

Results: Compared to wild-type littermates, EAAT3 heterozygous male mice have unaltered baseline anxiety-like, compulsive-like behavior and locomotor activity. Administration of acute amphetamine (5 mg/kg intraperitoneally) increased locomotion with no differences across genotypes. Tissue levels of glutamate, GABA, dopamine and serotonin did not vary between EAAT3 heterozygous and wild-type mice.

Conclusions: Our results indicate that reduced EAAT3 expression does not impact neurotransmitter content in the corticostriatal circuit nor alter anxiety or compulsive-like behaviors.

Keywords: EAAT3; Neuronal glutamate transporter; Obsessive–compulsive disorder; SLC1A1.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Excitatory Amino Acid Transporter 3 / genetics
  • Excitatory Amino Acid Transporter 3 / metabolism*
  • Genotype
  • Glutamic Acid / genetics
  • Glutamic Acid / metabolism*
  • Heterozygote
  • Male
  • Mice
  • Obsessive-Compulsive Disorder / genetics
  • Obsessive-Compulsive Disorder / metabolism*

Substances

  • Excitatory Amino Acid Transporter 3
  • SLC1A1 protein, human
  • Glutamic Acid