TY - JOUR
T1 - Neurochemical and behavioral characterization of neuronal glutamate transporter EAAT3 heterozygous mice
AU - González, Luis F.
AU - Henríquez-Belmar, Francisca
AU - Delgado-Acevedo, Claudia
AU - Cisternas-Olmedo, Marisol
AU - Arriagada, Gloria
AU - Sotomayor-Zárate, Ramón
AU - Murphy, Dennis L.
AU - Moya, Pablo R.
N1 - Funding Information:
This work was mainly supported by FONDECYT Grant 1141272 (PRM); the Intramural Research Program from the National Institute of Mental Health, NIH, Bethesda, USA (DLM); Millennium Nucleus NUMIND (NC130011) from the Millennium Scientific Initiative of the Ministry of Economy, Development and Tourism, Chile (PRM and GA), and FONDECYT Grant 11600398 (RSZ). Funding Agencies had no role in the study design, data collection/interpretation or writing of this manuscript. Not applicable
Publisher Copyright:
© The Author(s) 2017.
PY - 2017/9/19
Y1 - 2017/9/19
N2 - 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.
AB - 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.
KW - EAAT3
KW - Neuronal glutamate transporter
KW - Obsessive–compulsive disorder
KW - SLC1A1
UR - http://www.scopus.com/inward/record.url?scp=85039852996&partnerID=8YFLogxK
U2 - 10.1186/s40659-017-0138-3
DO - 10.1186/s40659-017-0138-3
M3 - Article
C2 - 28927446
AN - SCOPUS:85039852996
SN - 0716-9760
VL - 50
JO - Biological Research
JF - Biological Research
IS - 1
M1 - 29
ER -