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iNOS contribution to the NMDA‐induced excitotoxic lesion in the rat striatum
Author(s) -
Lecanu L,
Verrecchia C,
Margaill I,
Boulu R G,
Plotkine M
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702119
Subject(s) - microdialysis , nmda receptor , striatum , lesion , excitotoxicity , nitric oxide synthase , glutamate receptor , nitric oxide , chemistry , quinolinic acid , medicine , pharmacology , anesthesia , endocrinology , central nervous system , dopamine , pathology , biochemistry , tryptophan , receptor , amino acid
1 The aim of this study was to assess whether an excitotoxic insult induced by NMDA may induce an iNOS activity which contributes to the lesion in the rat striatum. 2 For this purpose, rats were perfused with 10 m M NMDA through a microdialysis probe implanted in the left striatum. Microdialysate nitrite content, striatal Ca‐independent nitric oxide synthase activity and lesion volume were measured 48 h after NMDA exposure in rats treated with dexamethasone (DXM) (3 mg kg −1 ×4) or aminoguanidine (AG) (100 mg kg −1 ×4). 3 A significant increase in microdialysate nitrite content and in the Ca‐independent NOS activity was observed 48 h after NMDA infusion. Both these increases were reduced by DXM and AG. The NMDA‐induced striatal lesion was also reduced by both treatments. 4 Our results demonstrate that NMDA excitotoxic injury induces a delayed, sustained activation of a Ca‐independent NOS activity. This activity is blocked by DXM and AG, strongly suggesting the involvement of iNOS. The fact that AG and DXM reduce the NMDA‐elicited lesion suggests that iNOS contributes to the brain damage induced by excitotoxic insult.British Journal of Pharmacology (1998) 125 , 584–590; doi: 10.1038/sj.bjp.0702119