2011 Volume 34 Issue 5 Pages 666-670
Theophylline-associated convulsions are frequently exacerbated by fever, but the mechanisms behind it are still not completely understood. We investigated whether N-methyl-D-aspartic acid (NMDA) and gamma aminobutyric acid (GABA) receptors are involved in aminophylline (theophylline-2-ethylenediamine)-induced convulsions that are augmented by heat exposure-induced hyperthermia in mice. Mice exposed to 33 °C temperatures for 2 h had significantly increased body temperature (0.94 °C). Heat exposure significantly decreased time required for the onset of convulsions induced by an intraperitoneal (i.p.) injection of aminophylline (300 mg/kg). The shortened time for onset of convulsions was blocked by the NMDA receptor antagonist dizocilpine (0.1, 0.3 mg/kg, i.p.). However, the GABAA receptor agonist muscimol (1, 2 mg/kg, i.p.) did not have any effect. The pro-convulsant action of NMDA (100—125 mg/kg, i.p.) was enhanced by the heat exposure of 33 °C. However, the pro-convulsant actions of picrotoxin (3—4 mg/kg, i.p.), a GABAA receptor antagonist, were not affected by increased temperatures. These results suggest that NMDA receptors in the brain play a role in aminophylline-induced convulsions, which are augmented by heat exposure-induced hyperthermia in mice.
