Journal
NEUROSCIENCE
Volume 394, Issue -, Pages 220-231Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2018.10.031
Keywords
5-HT2A receptors; TC-2153; head-twitches; depression; antidepressant; striatal-enriched protein tyrosine phosphatase
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Funding
- RFBR [16-34-00466, 16-54-12016]
- Basic Research Project [0324-2018-0016]
- Russian Ministry of Education and Science [2016-14-N08-0024, 14.N08.11.0085, RFMEFI62117X0015]
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The serotoninergic 5-HT2A receptor is involved in the mechanism of depression and antidepressant drugs action. Earlier we showed that striatal-enriched protein tyrosine phosphatase (STEP) inhibitor - 8-(trifluor omethyl)-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride (TC-2153) affects both the brain serotoninergic system and the brain-derived neurotropic factor that are known to be involved in the psychopathology of depression. In the present study we investigated the effects of chronic TC-2153 administration on behavior in the standard battery of tests as well as the effects of acute and chronic TC-2153 treatment on the brain 5-HT2A receptors in mice. We obtained a prominent antidepressant-like effect of chronic TC-2153 treatment in the forced swim test without any adverse side effects on locomotor activity, anxiety, exploration, motor skill and obsessive-compul sive-like behavior. Moreover, both acute and chronic TC-2153 administration inhibited the functional activity of 5-HT2A receptors estimated by the number of 2,5-dimethoxy-4-iodoamphetamine ( DOI , agonist of 5-HT2A receptors)-induced head-twitches. TC-2153 treatment also attenuated the DOI -induced c-fos expression in cortical and hippocampal neurons and reduced the 5-HT2A receptor protein level in the hippocampus and frontal cortex, but not in the striatum. Taken together, our combined data demonstrate that the antidepressant effect of STEP inhibitor TC-2153 could be mediated by its inhibitory properties towards the 5-HT2A receptor-mediated signaling. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.
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