Experimental spike-and-wave discharges induced by pentylenetetrazol and tolerance to repeated injections: an electrophysiological and biochemical study.
This study was designed to obtain experimental data to correlate duration of spike-and-wave (SW) paroxysms with levels of pentylenetetrazol (PTZ) in several brain regions after intraperitoneal (i.p.) administration of subconvulsive doses of PTZ in Wistar rats. The influence of subconvulsive doses of PTZ on blood-brain barrier (BBB) permeability and tolerance of PTZ to repeated injections were also studied. Intraperitoneal administration of subconvulsive doses of PTZ (25 mg/kg) in single doses resulted in SW activity which accounted for 20% of the continuous electrical brain activity recorded during the first hour after i.p. administration. Brain PTZ levels (cortex, midbrain, cerebellum) were within the range 19.2-34.9 micrograms/g. Repeated doses of PTZ showed a significant decrease in SW activity with no change in PTZ brain levels. As PTZ bioavailability was the same after either a single dose or after repeated doses, the decrease in SW activity may be due to PTZ tolerance. No alterations in the BBB were induced by PTZ subconvulsive doses. The experimental data reported in this study may be useful to quantify modifications of biochemical parameters or to evaluate antiepileptic drugs.