Cerebral ischemia decreases the behavioral effects and mortality rate elicited by activation of NMDA receptors in mice.
The purpose of this study was to determine whether prior transient cerebral ischemia, in conscious mice, would alter the biological responses resulting from excessive activation of N-methyl-D-aspartate (NMDA) receptors, in an early stage. The responses to the activation of NMDA receptors by an intracerebroventricular injection of NMDA, such as wild running, tonic and clonic convulsions, absence of the visual placing reflex, loss of the righting reflex, impaired motor function and a high mortality rate, were to a large extent prevented if 30 min before treatment, either a 10-min period of global cerebral ischemia was induced or a 1 nmol intraventricular injection of NMDA was given but not if either of the above procedures was done one day before the test dose of NMDA. In contrast, behavioral symptoms, in response to activation of non-NMDA-type glutamate receptors elicited by intraventricular injection of either kainic acid or AMPA, were not clearly affected. Transient systemic hypercapnic anoxia (22-sec exposure to 100% CO2 gas), before treatment with NMDA did not significantly reduce the NMDA-induced behavior. The severity of these behavioral responses and high mortality rate observed after intraventricular injection of pentylenetetrazole (PTZ, 30 mumol) were not altered by either prior global ischemic insult or by a preexposure to NMDA given intraventricularly. The NMDA antagonist, MK801 (0.1 and 0.3 mg/kg i.p.) greatly reduced the behavioral effects and mortality rate, resulting from the intraventricular injection of NMDA and somewhat reduced the effects of the intraventricular injection of PTZ.(ABSTRACT TRUNCATED AT 250 WORDS)
Himori
N
N
Department of Pharmacology, Nippon Roche Research Center, Kamakura, Japan.
Moreau
J L
JL
Martin
J R
JR
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002245:Carbon Dioxide / Q000633:toxicity; D016291:Dizocilpine Maleate / Q000633:toxicity; D005260:Female; D000860:Hypoxia / Q000523:psychology; D007276:Injections, Intraventricular; D002546:Ischemic Attack, Transient / Q000523:psychology*; D051379:Mice; D008815:Mice, Inbred Strains; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000633:toxicity*; D009410:Nerve Degeneration / Q000502:physiology*; D010433:Pentylenetetrazole / Q000633:toxicity; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D015996:Survival Rate
D016194:Receptors, N-Methyl-D-Aspartate; D002245:Carbon Dioxide; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D010433:Pentylenetetrazole