Improvement of cognitive dysfunction by a novel phosphodiesterase type 5 inhibitor, Tadalafil.

Abstract

There is substantial evidence for the modulatory role of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterases (PDEs) in memory and synaptic plasticity, and an increase in intracellular cGMP facilitates these processes. The present study was aimed at the neuropharmacological investigations of tadalafil (TAD 5, 10, and 20 mg/kg, p.o.) and further involvement of nitric oxide (NO)-cGMP in its effects. The effects of tadalafil and its combination with NG -nitro-L-arginine methyl ester (L-NAME) were investigated in scopolamine- and diabetes-induced cognitive dysfunction using elevated plus maze (EPM) and object recognition (ORT) tests. The results of EPM revealed that the scopolamine- and diabetes-induced learning and memory deficit was dose dependently attenuated after administration of TAD (TAD 10 and 20 mg/kg, p.o.) in both paradigms studied. Administration of L-NAME (20 mg/kg) aggravated scopolamine- and diabetes-induced learning and memory deficit. Co-administration of L-NAME (20 mg/kg) after TAD (20 mg/kg) produced significant increase in cognitive performance as compared to scopolamine- and diabetic- control group. This showed that L-NAME (20 mg/kg) aggravated scopolamine- and diabetes-induced learning and memory deficit was significantly reversed by TAD (20 mg/kg). The results of the present study revealed that tadalafil by inhibiting PDE5 possibly elevated the cGMP level that through a diversity of its substrates produced neuropharmacological effects in cognitive dysfunction.