First Author | Koshimizu H | Year | 2019 |
Journal | Neuropsychopharmacol Rep | Volume | 39 |
Issue | 1 | Pages | 56-60 |
PubMed ID | 30472790 | Mgi Jnum | J:293625 |
Mgi Id | MGI:6453281 | Doi | 10.1002/npr2.12041 |
Citation | Koshimizu H, et al. (2019) Comprehensive behavioral analysis and quantification of brain free amino acids of C57BL/6J congenic mice carrying the 1473G allele in tryptophan hydroxylase-2. Neuropsychopharmacol Rep 39(1):56-60 |
abstractText | AIM: Tryptophan hydroxylase 2 (Tph2) is a rate-limiting enzyme for the biosynthesis of 5-hydroxytryptamine (5-HT, serotonin). Previous studies have reported that C1473G polymorphism of the murine Tph2 gene leads to decreased 5-HT levels in the brain and abnormal behavioral phenotypes, such as impaired anxiety- and depression-like behaviors. In this study, to confirm the effect of the C1473G polymorphism on mouse phenotypes, we conducted a comprehensive battery of behavioral tests and measured the amounts of brain free amino acids involved in the production of 5-HT. METHODS: We obtained C57BL/6J congenic mice that were homozygous for the 1473G allele of Tph2 (1473G) and subjected them and their wild-type littermates (1473C) to a battery of behavioral tests. Using reverse-phase high-performance liquid chromatography (HPLC), we measured the amounts of free amino acids in the 5-HT and epinephrine synthetic/metabolic pathways in the frontal cortex, hippocampus, striatum, and midbrain. RESULTS: We failed to detect significant differences between genotypes in depression-like behaviors, anxiety-like behaviors, social behaviors, sensorimotor gaiting, or learning and memory, while 1473G mice exhibited a nominally significant impairment in gait analysis, which failed to reach study-wide significance. In the HPLC analysis, there were no significant differences in the amounts of 5-HT, dopamine, norepinephrine, and epinephrine in the frontal cortex, hippocampus, striatum, and midbrain. CONCLUSION: Our findings do not support the idea that congenic C57BL/6J mice carrying the 1473G allele may represent an animal model of mood disorder under normal conditions without stress. |