Inhibitor of Striatal-Enriched Protein Tyrosine Phosphatase, 8-(Trifluoromethyl)-1,2,3,4,5-Benzopentathiepin-6-Amine hydrochloride (TC-2153), Produces Antidepressant-Like Effect and Decreases Functional Activity and Protein Level of 5-HT2A Receptor in the Brain

Inhibitor of Striatal-Enriched Protein Tyrosine Phosphatase, 8-(Trifluoromethyl)-1,2,3,4,5-Benzopentathiepin-6-Amine hydrochloride (TC-2153), Produces Antidepressant-Like Effect and Decreases Functional Activity and Protein Level of 5-HT2A Receptor in the Brain Full article

Journal

Neuroscience
ISSN: 0306-4522 , E-ISSN: 1873-7544

Output data

Year: 2018, Volume: 394, Pages: 220-231 Pages count : 12 DOI: 10.1016/j.neuroscience.2018.10.031

Tags

5-HT2A receptors; TC-2153; head-twitches; depression; antidepressant; striatal-enriched protein tyrosine phosphatase

Authors

Kulikova E.A. ¹ , Khotskin N., V ¹ , Illarionova N.B. ¹ , Sorokin I.E. ¹ , Bazhenova E.Y. ¹ , Kondaurova E.M. ¹ , Volcho K.P. ² , Khomenko T.M. ² , Salakhutdinov N.F. ² , Ponimaskin E. ³ , Naumenko V.S. ¹ , Kulikov A.V. ¹

Affiliations

1	(Данные Web of science) Russian Acad Sci, Siberian Div, Inst Cytol & Genet, Fed Res Ctr, Novosibirsk, Russia
2	(Данные Web of science) Russian Acad Sci, Novosibirsk Inst Organ Chem, Siberian Div, Novosibirsk, Russia
3	(Данные Web of science) Hannover Med Sch, Cellular Neurophysiol, Hannover, Germany

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.

Kulikova E.A. , Khotskin N.,.V. , Illarionova N.B. , Sorokin I.E. , Bazhenova E.Y. , Kondaurova E.M. , Volcho K.P. , Khomenko T.M. , Salakhutdinov N.F. , Ponimaskin E. , Naumenko V.S. , Kulikov A.V.
Inhibitor of Striatal-Enriched Protein Tyrosine Phosphatase, 8-(Trifluoromethyl)-1,2,3,4,5-Benzopentathiepin-6-Amine hydrochloride (TC-2153), Produces Antidepressant-Like Effect and Decreases Functional Activity and Protein Level of 5-HT2A Receptor in the Brain
Neuroscience. 2018. V.394. P.220-231. DOI: 10.1016/j.neuroscience.2018.10.031 WOS Scopus РИНЦ

Published print:

Dec 1, 2018

Web of science	WOS:000451069300018
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Elibrary	38636587
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