CHRONIC ADMINISTRATION OF AN ANTICONVULSANT DOSE OF IMIDAZENIL FAILS TO INDUCE TOLERANCE OF GABA(A) RECEPTOR FUNCTION IN MICE

The ability of an anticonvulsant dose (0.1 mg/kg i.p.) of imidazenil, a new partial agonist of benzodiazepine receptors, to antagonize the c onvulsions and the increase in t-[S-35]butylbicyclophosphorothionate ( [S-35]TBPS) binding to the gamma-aminobutyric acid type A (GABA(A)) re ceptor elicited by isoniazid, an inhibitor of central GABAergic functi on, was evaluated in mice chronically treated (3 times daily for 30 da ys) with the same dose of imidazenil. The challenge dose of imidazenil , administered 36 h after the last injection of the chronic treatment protocol, reduced both isoniazid-induced convulsions and the isoniazid -induced increase in [S-35]TBPS binding to the same marked extent as i n control mice. These results indicate that long-term treatment with a pharmacologically effective dose of imidazenil failed to induce toler ance to both the anticonvulsant effect and the positive modulatory act ion on GABA(A) receptor function of this drug in mouse brain.