Association between tryptophan hydroxylase-2 genotype and the antidepressant effect of citalopram and paroxetine on immobility time in the forced swim test in mice

Tryptophan hydroxylase-2 (TPH2) is the rate limiting enzyme of serotonin synthesis in the brain. The 1473G allele of the C1473G polymorphism in mTPH2 gene is associated with reduced enzyme activity and serotonin synthesis rate in the mouse brain. Here, the influence of the 1473G allele on the antide...

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Published in:Pharmacology, biochemistry and behavior biochemistry and behavior, 2011-10, Vol.99 (4), p.683-687
Main Authors: Kulikov, Alexander V., Tikhonova, Maria A., Osipova, Daria V., Kulikov, Victor A., Popova, Nina K.
Format: Article
Language:English
Subjects:
Alleles
Animals
Antidepressive Agents, Second-Generation - pharmacology
C1473G polymorphism
Citalopram
Citalopram - pharmacology
Congenic mice
Dose-Response Relationship, Drug
Forced swim test
Male
Mice
Mice, Inbred C57BL
Motor Activity - drug effects
Paroxetine
Paroxetine - pharmacology
Polymorphism, Genetic - genetics
Polymorphism, Genetic - physiology
Serotonin Uptake Inhibitors - pharmacology
Swimming - psychology
Tryptophan Hydroxylase - genetics
Tryptophan hydroxylase-2
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Summary:Tryptophan hydroxylase-2 (TPH2) is the rate limiting enzyme of serotonin synthesis in the brain. The 1473G allele of the C1473G polymorphism in mTPH2 gene is associated with reduced enzyme activity and serotonin synthesis rate in the mouse brain. Here, the influence of the 1473G allele on the antidepressant effect of selective serotonin reuptake inhibitors (SSRIs), citalopram (2.5 or 5.0mg/kg) and paroxetine (5.0 or 10.0mg/kg), in the forced swim test was studied using B6-1473G and B6-1473C congenic mouse lines with the 1473G (decreased TPH2 activity) or 1473C (normal TPH2 activity) alleles, respectively, transferred to the genome of C57BL/6 mouse strain. Paroxetine (5.0 or 10.0mg/kg) and citalopram (2.5 or 5.0mg/kg) decreased immobility time in B6-1473C mice, while both doses of paroxetine and 2.5mg/kg of citaloprame did not alter immobility time in B6-1473G mice. However, 5.0mg/kg of citalopram reduced immobility in B6-1473G mice. The results provided genetic evidence of moderate association between 1473G allele and reduced sensitivity to SSRIs in mice. ► Effect of C1473G polymorphism on sensitivity to SSRIs was studied on congenic mice. ► The 1473G allele attenuated response to citalopram or paroxetine in forced swim test.
ISSN:0091-3057
1873-5177
DOI:10.1016/j.pbb.2011.06.020