The acute and subchronic pretreatment with antiepileptic drugs modifies the pentylenetetrazol- induced generalized seizures in mice .

Abstract

Objetives: The increased GABA content or administration of a centrally active GABA-mimetic agent have been used as a efficacious anticonvulsant therapeutic approach. However, it has been suggested that the use of drugs that continually and noncontingently alter synaptic transmission could alter at the nervous system. The present study was carried out to investigate the effects of acute (one administration) and subchronic (7 daily administrations) treatments with Diazepam (DZP; 10 mg/kg, ip), Gabapentin (GBP, 100 mg/kg. vo) and Vigabatrin (VGB, 500 mg/kg, vo) on pentylenetetrazol-induced generalized seizures (PTZ, 80 mg/kg, ip). Materials and methods: Male Taconic mice (20-25 g) received acute or subchronic treatment with DZP, VGB or GBP and 24 h after the last administration, the effects of PTZ (latency to the clonus, forelimb extension and death incidence) were evaluated. Results: Acute DZP protected all animals (100%) to the convulsant effects of PTZ, whereas subchronic DZP decreased the latency to the clonic (21%; p< 0.05), tonic (27%, p< 0.05) and death (37%, p< 0.05). The acute treatment with VGB protect all animals (100%) to the effects of PTZ, whereas its subcronic administration enhanced the latency to clonus (32%, p< 0.05), but facilitated the appearance of tonic seizures (55%, p< 0.05) and death (58%, p< 0.05). The acute administration of GPB increased the latency to clonus (52%, p< 0.05), whereas its subchronic treatment did not modify the PTZ-induced effects Conclusions: The present results indicate that the acute pretreatment with drugs enhancing GABAergic transmission differently modifies the seizure susceptibility, and that the subchronic administration may facilitate the seizure activity.