The influence of CGP-40116 on bicuculline evoked seizures in mice exposed to transient episode of brain oligemia.
To assess the role of NMDA receptors in the modulation of a brain tolerance after a transient cerebral mild ischemia, adult mice were exposed for 30 min to bilateral clamping of the common carotid arteries (BCCA) under pentobarbital anaesthesia. The competitive NMDA antagonist CGP-40116 was administered intraperitoneally (i.p.) in two experimental paradigms: a) acute treatment: twice, 4.0 mg/kg; 1.5 hour before the clamping of vessels and 6 hours after re-circulation and b) chronic treatment in a dose of 1.0 mg/kg; started 24 hours after re-circulation and continued once daily for 13 days with the last injection 24 hours before the induction of convulsions. Seizures were evoked with bicuculline (3.5 mg/kg, i.p.) 14 days after BCCA. Transient brain oligemia induced protection against bicuculline toxicity. The acute treatment with CGP-40116 only partially diminished the anticonvulsant phenomenon. In contrast, the chronic treatment with the drug markedly potentiated the effect. It can be concluded that NMDA receptors only partially participate in the induction of a protective effect against bicuculline toxicity after BCCA. The chronic treatment with low doses of the NMDA antagonist may enhance the brain tolerance, possibly due to the chemical preconditioning.
Rejdak
K
K
Department of Hygiene, Medical University, Lublin, Poland. maria@asklepios.am.lubin.pl
Rejdak
R
R
Czuczwar
S J
SJ
Kleinrok
Z
Z
Sieklucka-Dziuba
M
M
D015763:2-Amino-5-phosphonovalerate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001640:Bicuculline; D003292:Convulsants; D004198:Disease Susceptibility; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D002546:Ischemic Attack, Transient / Q000401:mortality / Q000473:pathology / Q000503:physiopathology*; D019194:Ischemic Preconditioning; D051379:Mice; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D013997:Time Factors
D000927:Anticonvulsants; D003292:Convulsants; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; C064539:2-amino-4-methyl-5-phosphono-3-pentenoic acid; D015763:2-Amino-5-phosphonovalerate; D001640:Bicuculline