Antiepileptic effects of amphetamine may require GABA (benzodiazepine) activity.
Secondary components of visual evoked potentials (slow negative wave-SNW, and photically-evoked sensory after discharge-SAD) are known to be precursors of experimentally activated wave-spike discharges, similar to wave-spikes of petit mal epilepsy. Both SNW and SAD may be potently suppressed either by amphetamine or GABAergic compounds such as diazepam and sodium valproate. A hypothesis was tested in the present study, that amphetamine-induced suppression of wave-spike discharges may require GABA-benzodiazepine activity for its expression. Electrocortical activity was recorded and averaged in unrestrained albino rats with chronically implanted epicortical electrodes. SNW and SAD obtained in habituated rats in the predrug state were potently suppressed by amphetamine (1 mg/kg, i.p.). Fifteen minutes after amphetamine injection, a challenging drug (metrazol, picrotoxin, convulsant benzodiazepine, Ro 5-3663, or imidazodiazepine, Ro 15-1788) was administered intraperitoneally. Subconvulsive doses of metrazol (10 mg/kg) reversed amphetamine suppression; imidazodiazepine (20 mg/kg) and picrotoxin (1.5 mg/kg) reliably opposed the SNW suppression; convulsant benzodiazepine, Ro 5-3663 (2 mg/kg), showed modest and nonsignificant effect in the same direction. It is proposed that the antiepileptic potency of amphetamine may be associated with its ability, apparently via modulatory effect of norepinephrine, to facilitate the activation of benzodiazepine-GABA receptors.
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants; D001569:Benzodiazepines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology; D005260:Female; D005442:Flumazenil; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D000927:Anticonvulsants; D001570:Benzodiazepinones; D001569:Benzodiazepines; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; C022193:Ro 5-3663; D000661:Amphetamine