Involvement of NMDA receptors in the beneficial effects of pioglitazone on scopolamine-induced memory impairment in mice
Autor: | Mina Almasi-Nasrabadi, Rosa Babaei, Shirin Mahdavian, Abbas Norouzi, Maedeh Sharifian, Ahmad Reza Dehpour, Mehrak Javadi-Paydar |
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Rok vydání: | 2012 |
Předmět: |
Agonist
medicine.medical_specialty medicine.drug_class Scopolamine Muscarinic Antagonists Receptors N-Methyl-D-Aspartate Mice Behavioral Neuroscience Memory Internal medicine Muscarinic acetylcholine receptor Avoidance Learning medicine Animals Hypoglycemic Agents Memory impairment Maze Learning Memory Disorders Pioglitazone business.industry Glutamate receptor Receptor antagonist Dizocilpine Endocrinology NMDA receptor Thiazolidinediones Dizocilpine Maleate business Excitatory Amino Acid Antagonists medicine.drug |
Zdroj: | Behavioural Brain Research. 231:138-145 |
ISSN: | 0166-4328 |
Popis: | Introduction Pioglitazone, a peroxisome proliferator activated receptor γ (PPARγ) agonist, is widely used in clinical medicine as a treatment for type 2 diabetes and is recently proved to have beneficial effects on improving cognition in early stages of Alzheimer's disease (AD). Moreover, it has been shown that pioglitazone reduces N-methyl- d -aspartate (NMDA, a glutamate agonist) mediated calcium currents and transients. Since enhanced calcium transients are present in AD models, we tested the hypothesis whether pioglitazone manifests its acquisition memory enhancement role through glutamatergic pathway. Material and methods Memory performance was evaluated in a two-trial recognition Y-maze test and passive avoidance in mice. Pioglitazone (20 or 40 mg/kg, p.o.) was administered 2 h before each trial, NMDA (75 mg/kg i.p.), 15 min before pioglitazone, and scopolamine, an M1 (muscarinic) receptor antagonist (0.3 or 1.0 mg/kg i.p.) and MK-801 (dizocilpine) (0.01, 0.03 or 0.1 mg/kg, i.p.), the highly selective, non-competitive NMDA antagonist – 30 min beforehand. Results (1) We induced the memory impairment by scopolamine or MK-801 before trials. (2) Pioglitazone did not improve the memory impairment induced by MK-801. (3) Pioglitazone significantly improved the memory impairment induced by scopolamine. (4) Subeffective dose of MK-801 nullified the beneficial effects of pioglitazone in scopolamine induced memory impaired mice. (5) NMDA promoted the effects of subeffective dose of pioglitazone on memory impaired by scopolamine. Discussion In conclusion, the present study suggests that glutamatergic pathway is involved in the pioglitazone induced memory performance. |
Databáze: | OpenAIRE |
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