A new synthetic varacin analogue, 8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride (TC-2153), decreased hereditary catalepsy and increased the BDNF gene expression in the hippocampus in mice

Abstract

Rationale: The creation of effective psychotropic drugs is the key problem of psychopharmacology. Natural compounds and their synthetic analogues attract particular attention.

Objectives: The effect of a new synthetic analogue of varacin, 8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride (TC-2153), on the behavior and the expression of the genes coding BDNF (Brain-Derived Neurotrophic Factor, Bdnf) and CREB (cAMP response element-binding protein, Creb) implicated in the mechanism of psychotropic drug action as well as gp130 (Il6st) implicated in the mechanism of hereditary catalepsy in the brain of mice of ASC (Antidepressant Sensitive Catalepsy) strain was studied.

Results: Acute per os administration of 20 or 40 mg/kg, but not 10 mg/kg of TC-2153 significantly decreased catalepsy. At the same time, in the open field test, 10 or 20 mg/kg of TC-2153 did not influence the locomotor activity, grooming or time spent in the center, while the highest dose of the drug (40 mg/kg) significantly reduced time in the center without any effect on locomotion and grooming. Chronic TC-2153 treatment (10 mg/kg for 12-16 days) did not influence the behavior in the open field but significantly attenuated catalepsy, increased Bdnf mRNA and decreased Il6st mRNA levels in the hippocampus.

Conclusions: The results suggest: 1) TC-2153 as a new drug with potential psychotropic and anticataleptic activities and 2) the involvement of BDNF and gp130 in the molecular mechanism of TC-2153 action.