Abstract
Accumulated evidence shows that the cAMP and cGMP signaling pathway plays an important
role in memory function and neuronal plasticity. Phosphodiesterase 5 (PDE5) is a hopeful
therapeutic target in AD (Alzheimer disease), and PDE5 inhibition may be a good therapeutic
strategy for the treatment of AD. In the present study, the four-day bilateral intra-hippocampal
infusion of H-89 as a protein kinase AII inhibitor (10 µM/side) and intra-peritoneal
injections of tadalafil (20 mg/kg) and scopolamine (0.5 mg/kg) alone and also on combination
on spatial learning in Morris water maze (MWM) were investigated. DMSO and saline
were used as controls for H-89 and other mentioned drugs, respectively. Rats were
trained for 4 days; each day included one block of four trials. Post- training probe
trial tests were performed on day 5. Administration of H-89 and scopolamine led to
a significant impairment in spatial learning compared to their related controls. But,
combination of tadalafil/H-89 or tadalafil/scopolamine reversed H-89 or scopolamine-
induced spatial learning deficits in MWM. Taken together, these results showed the
probable regulatory effects of cGMP on cholinergic and cAMP/PKA signaling pathways
in co-administrations of these mentioned drugs on spatial learning in MWM.
Key words
cGMP/PKG - morris water maze - spatial learning - PKA II inhibitor - scopolamine