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Publication : Reduced Vesicular Acetylcholine Transporter favors antidepressant behaviors and modulates serotonin and dopamine in female mouse brain.

First Author  Pádua-Reis M Year  2017
Journal  Behav Brain Res Volume  330
Pages  127-132 PubMed ID  28461009
Mgi Jnum  J:250450 Mgi Id  MGI:5920349
Doi  10.1016/j.bbr.2017.04.049 Citation  Padua-Reis M, et al. (2017) Reduced Vesicular Acetylcholine Transporter favors antidepressant behaviors and modulates serotonin and dopamine in female mouse brain. Behav Brain Res 330:127-132
abstractText  Depression is extremely harmful to modern society. Despite its complex spectrum of symptoms, previous studies have mostly focused on the monaminergic system in search of pharmacological targets. However, other neurotransmitter systems have also been linked to the pathophysiology of depression. In this study, we provide evidence for a role of the cholinergic system in depressive-like behavior of female mice. We evaluated mice knockdown for the vesicular acetylcholine transporter (VAChT KD mice), which have been previously shown to exhibit reduced cholinergic transmission. Animals were subjected to the tail suspension and marble burying tests, classical paradigms to assess depressive-like behaviors and to screen for novel antidepressant drugs. In addition, brain levels of serotonin and dopamine were measured by high performance liquid chromatography. We found that female homozygous VAChT KD mice spent less time immobile during tail suspension and buried less marbles, indicating a less depressive phenotype. These differences in behavior were reverted by central, but not peripheral, acetylcholinesterase inhibition. Moreover, female homozygous VAChT KD mice exhibited higher levels of dopamine and serotonin in the striatum, and increased dopamine in the hippocampus. Our study thus shows a connection between depressive-like behaviors and the cholinergic system, and that the latter interacts with the monoaminergic system.
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