Convulsant Properties of Cyclotrimethylenetrinitramine (RDX): Spontaneous, Audiogenic, and Amygdaloid Kindled Seizure Activity (Journal Version)

摘要

Dose-effect and time course relationships were determined for the effects of cyclotrimethylemetrinitramine (RDX) on seizure susceptibility. Male Long Evans rats treated with 0-60 mg/kg RDX, p.o., were monitored for spontaneous seizures during an 8 h interval between dosing and audiogenic (AG) seizure testing. Spontaneous and AG seizures were observed at dosages as low as 10-12.5 mg/kg. Spontaneous seizure incidence peaked at 2 h for all RDX treatment groups. In contrast, AG seizures (37.5 mg/kg) could be elicited only at 8 and 16 h, despite significant elevation of plasma RDX concentrations at 2 and 4 h. Because limbic system involvement was suggested by spontaneous seizure characteristics, the rate of amygdaloid kindling was measured following daily treatment with 6.0 mg/kg. The dosage significantly accelerated kindling development without inducing spontaneous seizures or producing an accumulation of RDX in plasma. These data provide preliminary evidence that limbic structures may participate in RDX induced seizure susceptibility. (Copyright (c) 1988 by Academic Press, Inc.)