In this study, we synthetized a series of 5-aryl-4,5-dihydrotetrazolo1,5- thieno2,3- pyridine derivatives containing tetrazole and other heterocycle substituents, i.e., triazole, methyltriazole, and triazolone. The forced swim test (FST) and tail suspension test (TST) were used to evaluate the antidepressant activity of the target compounds. The compound 5-4-(trifluoromethyl)phenyl-4,5-dihydrotetrazolo1,5- thieno2,3- pyridine ( ) showed the highest antidepressant activity, with a reduced immobility time of 55.33% when compared with the control group. Using an open-field test, compound was shown to not affect spontaneous activity of mice. The determination of in vivo 5-hydroxytryptamine (5-HT) concentration showed that compound may have an effect in the mouse brain. The biological activities of all synthetized compounds were verified by molecular docking studies. Compound showed significant interactions with residues of the 5-HT receptor homology model.