EFFECTS OF THE NITRIC OXIDE SYNTHASE INHIBITOR L-NAME ON RECOGNITION AND SPATIAL MEMORY DEFICITS PRODUCED BY DIFFERENT NMDA RECEPTOR ANTAGONIST IN THE RAT

Antonios Boultadakis (1) , Nikolaos Pitsikas (1)

1 Pharmacology

There is consistent experimental evidence that non-competitive antagonists of the 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. The present study was designed to investigate the ability of the NO synthase (NOS) 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 a) that L-NAME is sensitive to glutamate hypofunction produced by other than PCP NMDA antagonists such as MK-801 and ketamine and b) that L-NAME alone differentially affects rodents' spatial memory.

Mots clés: Psychopharmacology; Glutamate; Learning & Memory; Animal models; L-NAME; MK-801; recognition memory; spatial memory; rat

Antonios Boultadakis, Nikolaos Pitsikas. EFFECTS OF THE NITRIC OXIDE SYNTHASE INHIBITOR L-NAME ON RECOGNITION AND SPATIAL MEMORY DEFICITS PRODUCED BY DIFFERENT NMDA RECEPTOR ANTAGONIST IN THE RAT. Neuropsychopharmacology, 2010, ⟨10.1038/npp.2010.109⟩. ⟨hal-00558095⟩