Suppression of nitric oxide synthesis by L-NAME reverses the beneficial effects of pioglitazone on scopolamine-induced memory impairment in mice

• Published in: European journal of pharmacology 2011-01, Vol.650 (1), p.240-248
• Main Authors: Allami, Nika, Javadi-Paydar, Mehrak, Rayatnia, Farhoud, Sehhat, Kourosh, Rahimian, Reza, Norouzi, Abbas, Dehpour, Ahmad Reza
• Format: Article
• Language: English
• Subjects: acute effects; agonists; Alzheimer disease; Animals; Biological and medical sciences; cognition; Drug Interactions; L-NAME; Maze Learning - drug effects; Medical sciences; memory; Memory Disorders - chemically induced; Memory Disorders - enzymology; Memory Disorders - metabolism; Memory Disorders - physiopathology; Memory, Short-Term - drug effects; Mice; Motor Activity - drug effects; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide; Nitric Oxide - biosynthesis; nitric oxide synthase; Nitric Oxide Synthase - antagonists & inhibitors; noninsulin-dependent diabetes mellitus; pharmacology; Pharmacology. Drug treatments; Pioglitazone; scopolamine; Scopolamine Hydrobromide - pharmacology; Signal Transduction - drug effects; Spatial recognition memory; therapeutics; Thiazolidinediones - administration & dosage; Thiazolidinediones - pharmacology
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2010.10.007

Pioglitazone, an agonist of peroxisome proliferator-activated receptor gamma (PPARγ), which is widely used in treatment of type 2 diabetes, has shown some therapeutic effect in Alzheimer's disease. In this study, effects of acute pioglitazone on acquisition, consolidation and retrieval of memory, and also the involvement of nitric oxide (NO) in the effects of pioglitazone on spatial recognition memory has been investigated in a two-trial recognition Y-maze test and passive avoidance in mice. Memory impairment was induced by scopolamine (1 mg/kg, i.p.). Pioglitazone (10 and 20 mg/kg, p.o.) was administrated prior to either acquisition, consolidation or retention trials, while L-NAME (N-nitro- l-arginine methyl ester), a non-specific NO synthase inhibitor, was administered (10 mg/kg, i.p.) 30 min before each trial. Results: 1) pioglitazone improved the acquisition of recognition spatial memory-impaired by scopolamine; L-NAME dramatically reversed improving effects of pioglitazone on memory acquisition; 2) pioglitazone did not change the consolidation of spatial memory, impaired by scopolamine; 3) pioglitazone improved the retrieval of spatial memory and L-NAME did not alter the beneficial effect of pioglitazone; 4) pioglitazone did not affect scopolamine-induced cognitive impairments in the passive avoidance test. The present study demonstrates the beneficial effect of acute pioglitazone administration on acquisition and retrieval of scopolamine-induced cognitive deficits. This effect was reversed only in acquisition phase by nitric oxide synthase inhibitor, L-NAME, therefore, it could be concluded that NO might be involved in the pioglitazone beneficial effect of spatial memory acquisition.