Failure of chronic treatment with abecarnil to induce contigent and noncontingent tolerance in pentylenetetrazol-kindled rats.

ABSTRACT

We examined the effect of chronic treatment with abecarnil, a selective agonist at gamma-aminobutyric acid(A) (GABA(A)) receptors, on the development of tolerance to its anticonvulsant effect in pentylenetetrazole (PTZ)-kindled rats. We used two different experimental protocols to differentiate between pharmacological (noncontingent) and contingent tolerance. In one group of animals, kindling was suspended and abercarnil (1mg/kg intraperitoneally, i.p.) was administered three times daily for 15 days. In a second group of rats, PTZ-kindling was continued during chronic treatment with abecarnil. Tolerance to the anticonvulsant effect of a subsequent challenge dose of abecarnil (0.5 mg/kg i.p.) did not develop in either experimental group.