Effect of MK-801 on pilocarpine-evoked seizures in mice exposed to transient incomplete brain ischemia.
The aim of the study was to examine the role of NMDA receptors in the modulation of brain tolerance after transient cerebral ischemia. Adult mice were exposed for 30 min to bilateral clamping of common carotid arteries (BCCA) under anaesthesia. The non-competitive NMDA antagonist, MK-801 was administered intraperitoneally (ip) in two experimental paradigms: a) acute: twice at 1.0 mg/kg; 1 h before the clamping of the vessels and 6 h after re-circulation; b) chronic at a dose of 0.1 mg/kg, started 24 h after recirculation and continued once daily for 13 days with the last injection 24 h before the induction of convulsions. Seizures were evoked with pilocarpine (400 mg/kg, ip) 14 days after BCCA. It was found that transient incomplete brain ischemia induced protection against pilocarpine toxicity. The acute treatment with MK-801 did not diminish the anticonvulsant action of the procedure. In contrast, the chronic treatment with the drug led to a marked potentiation of the effect. In conclusion, it can be suggested that studied NMDA receptor antagonist used at relatively low dose may enhance the brain tolerance activated after a transient ischemic episode.
Rejdak
R
R
Department of Hygiene, Medical University, Lublin, Poland. robrej@hipokrates.am.lublin.pl
Rejdak
K
K
Sieklucka-Dziuba
M
M
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D002546:Ischemic Attack, Transient / Q000150:complications / Q000503:physiopathology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D018721:Muscarinic Agonists / Q000494:pharmacology*; D010862:Pilocarpine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*
D018691:Excitatory Amino Acid Antagonists; D018721:Muscarinic Agonists; D010862:Pilocarpine; D016291:Dizocilpine Maleate