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Drug Res (Stuttg) 2021; 71(05): 275-283
DOI: 10.1055/a-1345-7832
Original Article

Tadalafil Reversed H-89 – and Scopolamine – Induced Spatial Learning Impairments in Male Rats

Kaveh Tabrizian
1   Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran
2   Toxicology and Addiction Research Center, Zabol University of Medical Sciences, Zabol, Iran
,
Fatemeh Amelinia
3   Students Research Committee, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran
,
Maryam Belaran
4   Department of Physiology, Faculty of Medicine, Zabol University of Medical Sciences, Zabol, Iran
,
Soheil Pourheidar
5   Students Research Committee, Faculty of Medicine, Zabol University of Medical Sciences, Zabol, Iran
,
Hadi Mirzaei
6   Department of Biotechnology, Faculty of Medicine, Zabol University of Medical Sciences, Zabol, Iran
,
Sahar Fanoudi
7   Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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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


Publication History

Received: 15 August 2020

Accepted: 22 December 2020

Article published online:
15 January 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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