A Novel Azaindolizinone Derivative Zset1446 (Spiro[Imidazo[1,2-a]pyridine-3,2-indan]-2(3h)-one) Improves Methamphetamine-induced Impairment of Recognition Memory in Mice by Activating Extracellular Signal-regulated Kinase 1/2.
From: Laboratory of Neuropsychopharmacology, Division of Life Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa 920-1192, Japan.
The Journal of pharmacology and experimental therapeutics
- Publish Date: Feb 2007
- ISSN: 0022-3565
- Volume: 320
- Issue: 2
- Pages: 819-27
- Medium: Print
- Language: English
- Citation (JAMA): Ito Yukio, Takuma Kazuhiro, Mizoguchi Hiroyuki, et al. A Novel Azaindolizinone Derivative Zset1446 (Spiro[Imidazo[1,2-a]pyridine-3,2-indan]-2(3h)-one) Improves Methamphetamine-induced Impairment of Recognition Memory in Mice by Activating Extracellular Signal-regulated Kinase 1/2.. J. Pharmacol. Exp. Ther. Feb 2007;320:819-27
Abstract
The effect of ZSET1446 (spiro[imidazo[1,2-a]pyridine-3,2-indan]-2(3H)-one) on cognitive impairment in mice, previously treated with methamphetamine (METH) at a dose of 1 mg/kg for 7 days, was investigated. ZSET1446 showed a significant ameliorating effect on METH-induced impairment of recognition memory, although it had no effect on exploratory behavior. ZSET1446 (1 microg/kg) recovered the defect of the novelty-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in the prefrontal cortex (PFC) of METH-treated mice. The compound increased phosphorylated ERK1/2 levels in the hippocampus but not PFC of naive mice without affecting the total ERK1/2 levels. The ameliorating effect of ZSET1446 on recognition memory in METH-treated mice was negated by pretreatment with a mitogen-activated protein kinase/extracellular signal-regulated kinase kinase inhibitor, SL327 (alpha-[amino-(4-aminophenylthio)methylene]-2-(trifluoromethyl)phenylacetonitrile). Furthermore, the dopamine D1 receptor antagonist, SCH23390 [R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine], and N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 [5H-dibenzo[a,d]cyclohepten-5,10-imine (dizocilpine maleate)], blocked the ameliorating effect of ZSET1446 on METH-induced memory impairment, whereas the D2 receptor antagonist, raclopride, had no effect. These results suggest that the ameliorative effect of ZSET1446 on METH-induced memory impairment is associated with indirect activation of ERK1/2 following stimulation with dopamine D1 and NMDA receptors of the PFC. ZSET1446 would be a potential candidate for further preclinical study aimed at the treatment of cognitive deficits in Alzheimer’s disease and schizophrenia, as well as METH psychosis.
Mesh Headings (Keywords): (R)-2,3,4,5-Tetrahydro-8-chloro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol, Animals, Cognition, Dizocilpine Maleate, Enzyme Activation, Indans, Long-Term Potentiation, Male, Methamphetamine, Mice, Mice, Inbred ICR, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Prefrontal Cortex, Spiro Compounds
Check for Full Text / PubMed Unique Identifier (PMID): 17090702
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.