Research output: Contribution to journal › Article › peer-review
No effect of C1473G polymorphism in the tryptophan hydroxylase 2 gene on the response of the brain serotonin system to chronic fluoxetine treatment in mice. / Bazhenova, Ekaterina Y.; Sinyakova, Nadezhda A.; Kulikova, Elizabeth A. et al.
In: Neuroscience Letters, Vol. 653, 13.07.2017, p. 264-268.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - No effect of C1473G polymorphism in the tryptophan hydroxylase 2 gene on the response of the brain serotonin system to chronic fluoxetine treatment in mice
AU - Bazhenova, Ekaterina Y.
AU - Sinyakova, Nadezhda A.
AU - Kulikova, Elizabeth A.
AU - Kazarinova, Irina A.
AU - Bazovkina, Daria V.
AU - Gainetdinov, Raul R.
AU - Kulikov, Alexander V.
N1 - Publisher Copyright: © 2017 Elsevier B.V.
PY - 2017/7/13
Y1 - 2017/7/13
N2 - Selective serotonin reuptake inhibitors (SSRIs) are antidepressants that block serotonin transporter (SERT) and increase serotonin (5-HT) level in the synaptic cleft. The interaction between SERT and the key enzyme of 5-HT synthesis in the brain, tryptophan hydroxylase 2 (TPH2), is essential to maintain the brain 5-HT level. The G allele of C1473G polymorphism in Tph2 gene decreases enzyme activity by half in mouse brain. Here we studied effect of C1473G polymorphism on the reaction of brain 5-HT system to chronic fluoxetine treatment (120 mg/l in drinking water, for 3 weeks) in adult males of the congenic B6-1473C and B6-1473G mouse lines with high and low enzyme activity, respectively. The polymorphism did not affect the levels of 5-HT, its metabolite, 5-hydroxyindoleacetic acid (5-HIAA) and Tph2 gene mRNA in the brain. Fluoxetine significantly attenuated 5-HT levels in the cortex and striatum, 5-HIAA concentrations in the cortex, hippocampus, striatum and midbrain, and Tph2 gene expression in the midbrain. However, we did not observed any effect of the genotype x treatment interaction on these neurochemical characteristics. Therefore, C1473G polymorphism does not seem to play an essential role in the reaction of the brain 5-HT system to chronic fluoxetine treatment.
AB - Selective serotonin reuptake inhibitors (SSRIs) are antidepressants that block serotonin transporter (SERT) and increase serotonin (5-HT) level in the synaptic cleft. The interaction between SERT and the key enzyme of 5-HT synthesis in the brain, tryptophan hydroxylase 2 (TPH2), is essential to maintain the brain 5-HT level. The G allele of C1473G polymorphism in Tph2 gene decreases enzyme activity by half in mouse brain. Here we studied effect of C1473G polymorphism on the reaction of brain 5-HT system to chronic fluoxetine treatment (120 mg/l in drinking water, for 3 weeks) in adult males of the congenic B6-1473C and B6-1473G mouse lines with high and low enzyme activity, respectively. The polymorphism did not affect the levels of 5-HT, its metabolite, 5-hydroxyindoleacetic acid (5-HIAA) and Tph2 gene mRNA in the brain. Fluoxetine significantly attenuated 5-HT levels in the cortex and striatum, 5-HIAA concentrations in the cortex, hippocampus, striatum and midbrain, and Tph2 gene expression in the midbrain. However, we did not observed any effect of the genotype x treatment interaction on these neurochemical characteristics. Therefore, C1473G polymorphism does not seem to play an essential role in the reaction of the brain 5-HT system to chronic fluoxetine treatment.
KW - C1473G polymorphism
KW - Congenic mice
KW - Fluoxetine
KW - Serotonin
KW - Tryptophan hydroxylase 2
KW - HUMAN TRYPTOPHAN-HYDROXYLASE-2 GENE
KW - TPH2 GENE
KW - BEHAVIOR
KW - ASSOCIATION
KW - DEFICIENCY
UR - http://www.scopus.com/inward/record.url?scp=85020262065&partnerID=8YFLogxK
U2 - 10.1016/j.neulet.2017.05.070
DO - 10.1016/j.neulet.2017.05.070
M3 - Article
AN - SCOPUS:85020262065
VL - 653
SP - 264
EP - 268
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
ER -
ID: 9977395