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Effects of the nitric oxide synthase inhibitor L-NAME on recognition and spatial memory deficits produced by different NMDA receptor antagonists in the rat.

Authors
  • Boultadakis, Antonios
  • Pitsikas, Nikolaos
Type
Published Article
Journal
Neuropsychopharmacology
Publisher
Springer Nature
Publication Date
Nov 01, 2010
Volume
35
Issue
12
Pages
2357–2366
Identifiers
DOI: 10.1038/npp.2010.109
PMID: 20664579
Source
Medline
License
Unknown

Abstract

There is consistent experimental evidence that noncompetitive antagonists of the N-methyl-D-aspartate (NMDA) receptor, such as ketamine, MK-801, and phencyclidine (PCP), impair cognition and produce psychotomimetic effects in rodents. Nitric oxide (NO) is considered as an intracellular messenger in the brain. The implication of NO in learning and memory is well documented. This study was designed to investigate the ability of the NO synthase inhibitor L-NAME to antagonize recognition and spatial memory deficits produced by the NMDA receptor antagonists, MK-801 and ketamine, in the rat. L-NAME (1-3 mg/kg) counteracted MK-801- (0.1 mg/kg) and ketamine (3 mg/kg)-induced performance impairments in the novel object recognition task. L-NAME (10 mg/kg) attenuated ketamine (15 mg/kg)-induced spatial working memory and retention deficits in the radial water maze paradigm. L-NAME, applied at 3 mg/kg, however, disrupted rodents' performance in this spatial memory task. The present findings indicate (1) that L-NAME is sensitive to glutamate hypofunction produced by other than PCP NMDA antagonists such as MK-801 and ketamine and (2) that L-NAME alone differentially affects rodents' spatial memory.

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