title: Involvement of NMDA receptors in the beneficial effects of pioglitazone on scopolamine-induced memory impairment in mice.
abstract: BACKGROUND
  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.
  
  
  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 2h 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.
  
  
  CONCLUSIONS
  In conclusion, the present study suggests that glutamatergic pathway is involved in the pioglitazone induced memory performance.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mina
authors.initials: M
authors.lastname: Almasi-Nasrabadi
authors.forename: Mehrak
authors.initials: M
authors.lastname: Javadi-Paydar
authors.forename: Shirin
authors.initials: S
authors.lastname: Mahdavian
authors.forename: Rosa
authors.initials: R
authors.lastname: Babaei
authors.forename: Maedeh
authors.initials: M
authors.lastname: Sharifian
authors.forename: Abbas
authors.initials: A
authors.lastname: Norouzi
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D018727:Muscarinic Antagonists / Q000494:pharmacology; D000077205:Pioglitazone; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012601:Scopolamine / Q000494:pharmacology*; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007004:Hypoglycemic Agents; D018727:Muscarinic Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D045162:Thiazolidinediones; D016291:Dizocilpine Maleate; D012601:Scopolamine; D000077205:Pioglitazone