title: Tadalafil enhances working memory, and reduces hippocampal oxidative stress in both young and aged mice.
abstract: Tadalafil, a type-5 phosphodiesterase enzyme inhibitor with long half-life used to treat erectile dysfunction. Recently it has been reported that tadalafil improves cognitive function. Here, we aimed to investigate the age dependent effects of tadalafil on memory, locomotor, behavior, and oxidative stress in the hippocampus. Tadalafil was orally administered everyday (5 mg/kg) to young (2 months) and old (16 months) healthy mice for 4 weeks. Control mice from each group received equal volume of 0.9% normal saline for the same duration. Memory and locomotor activity were tested using radial arm maze and open field test respectively. The level of malondialdehyde (MDA), nitric oxide (NO), and advanced protein oxidation product (APOP) was analyzed and catalase activity was determined from the isolated hippocampus. Treatment with tadalafil in aged mice improves working memory than the corresponding tadalafil treated young mice in radial arm maze test. Tadalafil treated mice traveled less distance in the center and the mean speed of tadalafil treated aged mice was significantly lower than the tadalafil treated young mice in open field test. Tadalafil treatment elicited a decrease of MDA level in the hippocampus of aged mice than that of young mice. APOP level was decreased only in aged mice treated with tadalafil. Treatment with tadalafil decreased NO and increased catalase activity in both young and aged mice. On the basis of previous and our findings, we conclude that tadalafil treatment reduces oxidative stress while increased cGMP level in the hippocampus might be responsible for memory enhancement.
authors.affiliation: Department of Pharmaceutical Sciences, North South University, Bashundhara, Dhaka 1229, Bangladesh. Electronic address: alamin@northsouth.edu.
authors.forename: Md Mamun
authors.initials: MM
authors.lastname: Al-Amin
authors.affiliation: Department of Pharmaceutical Sciences, North South University, Bashundhara, Dhaka 1229, Bangladesh.
authors.forename: S M Nageeb
authors.initials: SM
authors.lastname: Hasan
authors.affiliation: Department of Pharmaceutical Sciences, North South University, Bashundhara, Dhaka 1229, Bangladesh.
authors.forename: Tanzir
authors.initials: T
authors.lastname: Alam
authors.affiliation: Department of Pharmaceutical Sciences, North South University, Bashundhara, Dhaka 1229, Bangladesh.
authors.forename: Ahmed Tasdid
authors.initials: AT
authors.lastname: Hasan
authors.affiliation: Department of Pharmaceutical Sciences, North South University, Bashundhara, Dhaka 1229, Bangladesh.
authors.forename: Imran
authors.initials: I
authors.lastname: Hossain
authors.affiliation: Department of Pharmaceutical Sciences, North South University, Bashundhara, Dhaka 1229, Bangladesh.
authors.forename: Rohini Rowshan
authors.initials: RR
authors.lastname: Didar
authors.affiliation: Department of Pharmaceutical Sciences, North South University, Bashundhara, Dhaka 1229, Bangladesh.
authors.forename: Md Ashraful
authors.initials: MA
authors.lastname: Alam
authors.affiliation: Department of Pharmaceutical Sciences, North South University, Bashundhara, Dhaka 1229, Bangladesh.
authors.forename: Md Mahbubur
authors.initials: MM
authors.lastname: Rahman
mesh_terms: D000375:Aging / Q000378:metabolism / Q000523:psychology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008570:Memory, Short-Term / Q000187:drug effects*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D018697:Nootropic Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D000068581:Tadalafil
chemical_list: D000975:Antioxidants; D002243:Carbolines; D018697:Nootropic Agents; D058986:Phosphodiesterase 5 Inhibitors; D009569:Nitric Oxide; D000068581:Tadalafil; D006152:Cyclic GMP
keywords: Hippocampus; Memory; Phosphodiesterase; Tadalafil