Effect of MK-801 and ketamine on hydroxyl radical generation in the posterior cingulate and retrosplenial cortex of free-moving mice, as determined by in vivo microdialysis.
This study investigated the effect of MK-801 and ketamine, N-methyl-D-aspartate (NMDA) receptor antagonists which can induce schizophrenic symptoms and have neurotoxicity in human and animals, on hydroxyl radical (*OH) generation in the posterior cingulate and retrosplenial (PC/RS) cortex of free-moving mice using the salicylic acid trapping technique. MK-801 (0.6 mg/kg) or ketamine (50 mg/kg) acute administration significantly increased *OH levels in mouse PC/RS cortex. The basal *OH levels after MK-801 and ketamine administrations for 7 consecutive days were significantly increased compared with the naive basal levels. MK-801 (0.6 mg/kg) or ketamine (50 mg/kg) challenge after chronic administration further significantly increased dialysate levels of *OH. Our study also found that the release of *OH was secondary to stereotyped behavior, and the intensity of stereotyped behavior induced by MK-801 was more than that induced by ketamine. The results suggested that NMDA receptor antagonists participate in the generation of *OH in the PC/RS cortex of mouse, and oxidative stress, derived from the formation of free radicals, might play an important role in the pathophysiology of these two models of schizophrenia.
Zuo
Dai-Ying
DY
Department of Pharmacology, Shenyang Pharmaceutical University, Mailbox 41, Wenhua Road 103, Shenyang, 110016, China.
Wu
Ying-Liang
YL
Yao
Wen-Xue
WX
Cao
Yue
Y
Wu
Chun-Fu
CF
Tanaka
Masatoshi
M
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002396:Catechols / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism*; D062385:Hydroxybenzoates; D017665:Hydroxyl Radical / Q000378:metabolism*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D017551:Microdialysis; D013239:Stereotyped Behavior / Q000187:drug effects
D002396:Catechols; D018691:Excitatory Amino Acid Antagonists; D062385:Hydroxybenzoates; D017665:Hydroxyl Radical; D007649:Ketamine; D016291:Dizocilpine Maleate; C009135:2,3-dihydroxybenzoic acid