Antiepileptogenic properties of phenobarbital: behavior and neurochemical analysis

Chronic in vivo models of epilepsy provide a suitable strategy for quantifying epileptogenesis, as well as investigating neurochemical changes associated with neuronal plasticity that leads to seizuring conditions. The aim of this paper was to investigate antiepileptogenic properties of phenobarbital, focusing on the neurochemical changes associated with repeated seizures induced by low convulsive dose of pentylenetetrazol (PTZ) (60 mg/kg, sc) in mice. Phenobarbital (10 and 30 mg/kg, ip) significantly diminished the severity of seizures induced by PTZ. Repeated PTZ administration was associated with an increase in [H-3]glutamate binding (B-max 196.6 +/- 10.2 pmol/mg x control B-max 137.7 +/- 17.0 pmol/mg). Regarding NMDA receptors, repeated PTZ administration was likewise associated with an increase in [H-3]MK-801 binding (0.55 +/- 0.02 pmol/mg x control 0.32 +/- 0.01 pmol/mg). In addition, phenobarbital (10 mg/kg) prevented the increase in [H-3]glutamate binding (B-max 133.7 +/- 11.4 pmol/mg), as well as in [H-3]MK-801 binding (phenobarbital 10 and 30 mg/kg, 0.33 +/- 0.01 and 0.34 +/- 0.01 pmol/ mg, respectively). This study reveals an interesting capability of phenobarbital in interfering with the establishment of both the behavioral expression and associated neurochemical changes induced by the repeated administration of low convulsive dose of PTZ, which may be important in the context of preventing epileptogenesis. (C) 2000 Elsevier Science Inc. All rights reserved.