Effects of seizures and antiepileptic drugs on benzodiazepine receptors in rat brain.

Abstract

Benzodiazepine receptors appear to be pharmacologically important as the modulator of anxiolytic, anticonvulsant, and muscle relaxant activities in the central nervous system. The acute effects of valproic acid (VPA), diazepam (DZ), phenobarbital (PB), and phenytoin (PHT) on benzodiazepine receptor binding as measured by 3H-flunitrazepam were studied in Sprague Dawley (S/D) rat cerebral cortices. The acute effects of seizures were also studied in both S/D rats and audiogenic seizure rats. In the VPA (100 mg/kg, IP) treated rats, there was a 11% increase in benzodiazepine receptor density (Bmax). This effect appear to be dose dependent as higher doses of VPA (200-500 mg/kg) resulted in more increase in Bmax. No significant change occurred in Kd after acute VPA treatment. However, acute PB (100 mg/kg), PHT (100-200 mg/kg), or DZ (50 mg/kg) did not produce any changes in Bmax or dissociation constants (Kd). In S/D rats, significant increases in Bmax were observed 30 minutes after seizures induced by electroshock or pentylenetetrazol (50 mg/kg) IP injection. However, audiogenic seizure rats had higher Bmax prior to the induction of seizures when compared to normal S/D rats, and no changes in Bmax occurred after seizures in audiogenic seizure rats. No changes in Kd were seen in either S/D rats or audiogenic seizure rats before and after seizures. These data suggest that an increase in benzodiazepine receptor density might correlate with the mechanism of anticonvulsant action of VPA, and that a possible disorder of the GABA/benzodiazepine receptor complex may be involved in the seizure susceptibility in audiogenic seizure rats.