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

Publication date: Available online 24 October 2018Source: NeuroscienceAuthor(s): E.A. Kulikova, N.V. Khotskin, N.B. Illarionova, I.E. Sorokin, E.Y. Bazhenova, E.M. Kondaurova, K.P. Volcho, T.M. Khomenko, N.F. Salakhutdinov, E. Ponimaskin, V.S. Naumenko, A.V. KulikovAbstractThe 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-(trifluoromethyl)-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-compulsive-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...
Source: Neuroscience - Category: Neuroscience Source Type: research