Suppression of nitric oxide synthesis by L-NAME reverses the beneficial effects of pioglitazone on scopolamine-induced memory impairment in mice.
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 (1mg/kg, i.p.). Pioglitazone (10 and 20mg/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 (10mg/kg, i.p.) 30min 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.
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Nika
N
Allami
Mehrak
M
Javadi-Paydar
Farhoud
F
Rayatnia
Kourosh
K
Sehhat
Reza
R
Rahimian
Abbas
A
Norouzi
Ahmad Reza
AR
Dehpour
D000818:Animals; D004347:Drug Interactions; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced* / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D008570:Memory, Short-Term / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D000077205:Pioglitazone; D012601:Scopolamine / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology*
D045162:Thiazolidinediones; D009569:Nitric Oxide; D012601:Scopolamine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D000077205:Pioglitazone