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Mice were exposed to 1 month of spaceflight on Russian biosatellite BION-M1 to determine its effect on the expression of key genes in the brain dopamine (DA) and serotonin (5-HT) systems. Spaceflight decreased the expression of crucial genes involved in DA synthesis and degradation, as well as the D1 receptor. However, spaceflight failed to alter the expression of tryptophan hydroxylase-2, 5-HT transporter, 5-HT1A, and 5-HT3 receptor genes, though it reduced 5-HT2A receptor gene expression in the hypothalamus. We revealed risk DA and 5-HT neurogenes for long-term spaceflight for the first time, as well as microgravity-responsive genes (tyrosine hydroxylase, catechol-O-methyltransferase, and D1 receptor in the nigrostriatal system; D1 and 5-HT2A receptors in the hypothalamus; and monoamine oxidase A (MAO A) in the frontal cortex). Decreased genetic control of the DA system may contribute to the spaceflight-induced locomotor impairment and dyskinesia described for both humans and rats.

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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We compared the effect of a new potential antidepressant 8-trifluoromethyl 1,2,3,4,5-benzopentathiepine-6-amine hydrochloride (TC-2153) and classical antidepressant fluoxetine in a dose of 0.25 mg/liter on the behavior of Danio rerio in the "novel tank" test and content of biogenic amines and their metabolites in the brain. Fluoxetine alone and TC-2153 alone significantly increased the time spent in the upper part of the tank and insignificantly reduced motor activity. Combined exposure of fishes in the solution containing potential and classical antidepressants potentiated their effects on both parameters. The compounds did not affect brain contents of serotonin, dopamine, and norepinephrine. At the same time, fluoxetine, but not TC-2153, reduced brain content of the main serotonin metabolite 5-hydroxyindole acetic acid.

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