Antidepressant-like effect of tadalafil, a phosphodiesterase type 5 inhibitor, in the forced swim test: Dose and duration of treatment dependence

Nitric oxide (NO), an intercellular messenger in central nervous system, plays an important role in the pathogenesis of major depression. Antidepressant-like effect of sildenafil, a phosphodiesterase 5 inhibitor (PDE5-I), at lower dose, but not at higher doses, was reported previously. Hence, present work was undertaken to study the effects of tadalafil (TAD), another PDE5-I, per se and in combination with L-NAME in forced swimming test (FST) in rat for 14 days. TAD (5 mg/kg, p.o.) significantly reduced immobility duration, increased swimming duration on day 1 and 14, and increased climbing frequency on day 14 as compared to normal group. Whereas, TAD (10 and 20 mg/kg, p.o.) insignificant in this regards. On day 1 and 14, L-NAME (20 mg/kg, i.p.) showed reduction in immobility duration and increase in swimming duration and climbing frequency. L-NAME (20 mg/kg) after TAD (20 mg/kg) reduced immobility duration and increased swimming duration on day 1 and 14 and increased climbing frequency on day 14 as compared to normal group. Tadlafil, at low dose but not at higher dose, has antidepressant-like effect on behavior in FST. L-NAME has antidepressant-like effect on behavior in FST. L-NAME does not interact with tadalafil (20 mg/kg) in regards of effects on behavior in FST. The results showed that, tadalafil produced dose dependent but time-independent effect on immobility and swimming whereas dose and time dependent effect on climbing was evident.