Lack of tolerance to anticonvulsant effects of clonazepam in a rat pentylenetetrazol (PTZ) induced kindled seizure model.

The development of tolerance to the anticonvulsant effects of clonazepam (CZP) was investigated using a pentylenetetrazol (PTZ)-induced kindled rat seizure model. PTZ kindled rats received twice daily injections, either 0.3 mg/kg of CZP for 3 weeks, 2.0 mg/kg of CZP for 2 weeks or vehicle (propylene glycol) as maintenance doses. PTZ injections (30 mg/kg) were given once weekly both prior to and after the initiation of maintenance doses. The protective effect of CZP against PTZ-induced seizures was examined by determining the protective effect of a single dose of CZP (0.1 or 0.3 mg/kg) given once weekly 30 min prior to 30 mg/kg PTZ injection. CZP treatment continued to protect the rats from kindled seizures during the CZP maintenance period in both experiments. No significant differences were found in seizure responses between rats receiving either dose of CZP maintenance and the vehicle maintenance control group (p > 0.05). We were unable to demonstrate tolerance to the protective effects of CZP against PTZ-induced kindled seizures in this rat seizure model.