Abstracts

Using a model of pentylenetetrazol (PTZ)-induced seizures we examined weather withdrawal of clonazepam (CZP) and/or partial benzodiazepine (BZs) agonist Ro 19-8022 leads to changes in seizure susceptibility in immature rats., To detect development of rebound phenomena, single dose of CZP (1 mg/kg i.p.) or Ro 19-8022 (0.5 mg/kg i.p.) was injected to P12 rats. Seizures were induced by PTZ in doses of 50 (sub-threshold) or 100 (supra-threshold) mg/kg s.c. 12, 24 or 48 h later. To assess changes of seizure susceptibility after chronic administration, animals received either BZ in doses mentioned above for 5 consecutive days starting at P7. PTZ (50 mg/kg s.c.) was injected 2, 4 or 6 d after the last BZ injection. Changes in sensitivity to anticonvulsant effects of BZs after treatment discontinuation were detected in additional groups of animals 1 or 2 days after the end of chronic treatment. Animals received fully anticonvulsant dose of CZP (0.08 mg/kg i.p.) or Ro 19-2088 (0.05 mg/kg i.p.) and 10 min later PTZ in a dose of 100 mg/kg s.c. Incidence and latency of generalized tonic-clonic seizures as well as severity of seizures were registered., After a single injection of tested BZs, anticonvulsant effects expressed as prolongation of GTCS latencies were still observed 12 h (Ro 19-8022) or 24 h (CZP) after injection. In intervals 24 and 48 h, respectively, latencies were however 40-60% shorter compared to untreated controls (p[lt]0.05). At the same time points, PTZ (50 mg/kg) induced more severe seizures (p[lt]0.01) with significantly higher incidence of GTCS in BZs-treated rats compared to controls (p[lt]0.05). Chronic administration of CZP increased both seizure severity and incidence of GTCS for 6 d after the last CZP injection compared to untreated controls (p[lt]0.05). In contrast, no changes in severity of epileptic phenomena were observed after chronic administration of Ro 19-8022. Neither CZP nor Ro 19-8022 administered chronically changed efficacy of BZs against seizures induced by PTZ (100 mg/kg s.c.) 1 or 2 d after the end of therapy., In immature rats, withdrawal of chronic CZP but not Ro 19-8022 treatment increased severity of PTZ-induced seizures. In contrast, single dose of both CZP and Ro19-8022 led to occurrence rebound phenomenon., (Supported by a research project No. LC554 of the Ministry of Education of the Czech Republic.)