Intermittent clonazepam treatment prevents anticonvulsant tolerance in mice

The influence of intermittent benzodiazepine treatment on anticonvulsant tolerance was studied by comparing mice treated either daily or on alternate days with clonazepam, 0.25 mg/kg, i.p., administered twice a day. Tolerance was assessed by the ability of clonazepam to prevent pentylenetetrazol (PTZ) induced clonic convulsions. In mice treated daily with clonazepam, significant tolerance was evident after 5 days of treatment but did not increase further after 10 or 20 days of treatment. However, mice treated with clonazepam only on alternate days for 10 or 20 days showed no tolerance. Our data indicate that intermittent treatment may prevent development of tolerance to the anticonvulsant action of benzodiazepines.