Mice and rats are sensitized to the proconvulsant action of a benzodiazepine-receptor inverse agonist (FG 7142) following a single dose of lorazepam.

Rats and mice were treated with lorazepam (1.0 mg/kg) or its vehicle. Six h later seizure threshold to i.v. pentylenetetrazole was determined following treatment with the benzodiazepine-receptor inverse agonist FG 7142, the antagonist Ro 15-1788 or a second dose of lorazepam. Although lorazepam alone was anticonvulsant 6 h after its administration, animals pretreated with lorazepam were more sensitive to the proconvulsant action of FG 7142 and less sensitive to the effects of a second treatment with lorazepam.