Effect of 1,3-di-o-tolylguanidine (DTG), rimcazole and EMD 57445, the sigma receptor ligands, in the forced swimming test.

As it is known, sigma receptor ligands have been able to modulate the central neurotransmitter systems, including noradrenergic-, NMDA-ergic- and dopaminergic ones, which are essential for the mechanism of action of antidepressant drugs. Therefore, it can be assumed that some selective sigma ligands can possess antidepressant-like activity. In the present studies 1,3-di-o-tolylguanidine (DTG), rimcazole (RIM) and EMD 57445 were examined in the forced swimming test in rats and mice. DTG and RIM decreased the immobility time in mice. EMD 57445 was inactive but it antagonized the anti-immobility effects of DTG and RIM. Both latter drugs did not change the locomotor activity of mice, EMD 57445 at higher dose decreased it. In addition, DTG showed antidepressant-like activity in rats, this effect being counteracted by EMD 57445. At the same time both drugs attenuated the spontaneous motor activity in rats. Taken together, the present results suggested that DTG and RIM may possess sigma agonistic activity while EMD 57445--the antagonistic one. Further investigations are needed to support agonistic/antagonistic activities of the studied sigma ligands and to elucidate the potential involvement of sigma site subtypes in this model.