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Background: Striatal-enriched Tyrosine Phosphatase (STEP) plays a key role in the mechanisms of neuronal signaling and is a potential molecular target for new generation of psychotropic drugs. STEP inhibitor, 8-(trifluoromethyl-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride (TC-2153), shows anxiolytic effect on mice. Zebrafish (Danio rerio) is a suitable model for the study of anxiety pharmacology. Objective: The objective of this study is to investigate the effects of acute and chronic TC-2153 treatment on zebrafish anxiety-related behavior. Methods: The effects of acute (0.125 and 0.25 mg/l, 3 h) and chronic (0.125 mg/l, 14 days) administration of TC-2153 on locomotion and anxiety-related behavior (time spent near the bottom and mean distance from the bottom) of adult zebrafish in the Novel Tank (NT) test were compared with those of the same doses of fluoxetine chosen as a positive control. Results: Acute treatment with 0.125 mg/l and 0.25 mg/l of TC-2153 or fluoxetine decreased time spent near the bottom, increased time spent near the surface and increased mean distance from the bottom of tank. Chronic treatment with 0.125 mg/l of TC-2153 reduced only time spent near the tank bottom without any effect on time spent near the surface and mean distance from the bottom, while chronic administration of 0.125 mg/l of fluoxetine altered these three indices of anxiety. Conclusion: Both acute and chronic TC-2153 produces anxiety-like effect indicating STEP involved in the mechanism of anxiety-related behavior in zebrafish. At the same time, chronic treatment with TC-2153 reduced locomotor activity. Zebrafish is a promising laboratory object to study the role of STEP in the nervous system.

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