The influence of MK-801 on bicuculline evoked seizures in adult mice exposed to transient episode of brain ischemia

• Published in: Journal of Neural Transmission Vol. 107; no. 8-9; pp. 947 - 957
• Main Authors: REJDAK, K, REJDAK, R, KLEINROK, Z, SIEKLUCKA-DZIUBA, M
• Format: Journal Article
• Language: English
• Published: Wien Springer 01.01.2000; New York, NY
• Subjects: Age Factors; Animals; Behavior, Animal - drug effects; Bicuculline; Biological and medical sciences; Brain Chemistry - drug effects; Convulsants; Dizocilpine Maleate - pharmacology; Epilepsy - chemically induced; Epilepsy - drug therapy; Epilepsy - etiology; Excitatory Amino Acid Antagonists - pharmacology; gamma-Aminobutyric Acid - analysis; gamma-Aminobutyric Acid - metabolism; Ischemic Attack, Transient - complications; Ischemic Attack, Transient - drug therapy; Ischemic Attack, Transient - mortality; Ischemic Preconditioning; Male; Medical sciences; Mice; Neurology; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - metabolism; Seizures - chemically induced; Seizures - drug therapy; Seizures - etiology; Survival Rate; Vascular diseases and vascular malformations of the nervous system; Nervous system diseases; Toxicity; Dizocilpine; Rodentia; Cardiovascular disease; Glutamate receptor; Transitory; Cerebral disorder; Vascular disease; Vertebrata; Experimental disease; Mammalia; Ischemia; Mouse; Animal; Central nervous system disease; Antagonist; NMDA receptor; Preconditioning; Cerebrovascular disease; Brain (vertebrata)
• ISSN: 0300-9564; 1435-1463
• DOI: 10.1007/s007020070044

The aim of the study was to examine the role of NMDA receptors in modulation of protective effect against bicuculline toxicity after transient brain ischemia in mice. Animals were exposed for 30 min to bilateral clamping of the common carotid arteries (BCCA) in anaesthesia. MK-801 was administered intraperitoneally in two paradigms: a) acute treatment: twice, 1.0 mg/kg; 1 hour before clamping and 6 hours after re-circulation and b) chronic treatment: 0.1 mg/kg; started 24 hours after re-circulation and continued once daily for 13 days, the last injection was administered 24 hours before seizure induction. 14 days after BCCA, the animals were injected with bicuculline (3.5 mg/kg s.c). A significant decrease in seizure susceptibility could be observed in BCCA treated mice compared with sham-operated controls. Acute treatment with MK-801 did not affect seizure activity both in sham and BCCA mice. Chronic treatment with the drug potentiated anticonvulsant effect of brain ischemia but had no influence on seizure activity in sham-operated mice. The analysis of GABA content in brain tissue performed 14 days after BCCA showed a moderate increase in vehicle-treated mice and significant elevation after chronic treatment with MK-801. It can be suggested that NMDA receptors are not involved in the induction of a protective effect against bicuculline toxicity after transient brain ischemia. The prolonged treatment with low doses of MK-801 may potentiate a developed process in a mechanism of chemical preconditioning.