The effects of new sigma (s) receptor ligands, PB190 and PB212, in the models predictive of antidepressant activity

Background: A number of s receptor ligands have been demonstrated to possess antidepressant-like effect in some experimental paradigms (e.g. forced swim test, tail suspension test, olfactory bulbectomy model, conditioned fear stress). The objective of the present study was to find out whether PB190 and PB212, new s1 receptor ligands, show the effects in some models predictive of antidepressant activity. Methods: The impact of PB190 and PB212 on the immobility time in the forced swim test (FST) and tail suspension test (TST) was assessed in C57BL/6J male mice. Extracellular bradykinin triggers a transient increase in intracellular calcium concentration by activating the phospholipase C/IP3 pathway. The intracellular calcium concentration was estimated with the dual wavelength ratiometric probe Fura-2. Results: In the FST model, PB190 showed a moderate antidepressant-like effect (only in the dose of 3 mg/ kg) which was enhanced by joint treatment with amantadine (AMA), 10 mg/kg (inactive per se). The decrease in the immobility time induced by the combined treatment with PB190 and AMA was counteracted by PB212 and by BD1047, a s1-receptor antagonist. The in vitro studies indicated that Ca 2+