Involvement of GABAergic mechanisms in chloroquine-induced seizures in mice

1. The influence of some GABAergic agents on tonic seizures elicited by chloroquine was investigated in mice. 2. Chloroquine (45-100 mg/kg) elicited seizures in mice in a dose related manner. 3. Muscimol (1-2 mg/kg), DABA (8-16 mg/kg) and baclofen (4-16 mg/kg) profoundly delayed the onset of chloroquine (65 mg/kg)-induced seizures. The incidence of the seizures was also significantly reduced by muscimol (1-2 mg/kg), DABA (8 mg/kg) and baclofen (4-8 mg/kg). 4. AOAA (10 mg/kg) profoundly reduced the proportion of mice that convulsed while AOAA (20 mg/kg) completely protected mice against chloroquine (65 mg/kg)-induced seizures. 5. Bicuculline (5 mg/kg) and picrotoxin (0.5-1 mg/kg) significantly potentiated chloroquine (50 mg/kg)-induced seizures. The onset of seizures and the number of mice that convulsed were shortened and increased respectively. The onset of chloroquine (65 mg/kg)-elicited seizures was also profoundly shortened. Bicuculline (5 mg/kg) and picrotoxin (0.5 mg/kg) effectively antagonised the protective effects of muscimol (2 mg/kg), AOAA (10 mg/kg) and DABA (8 mg/kg) against chloroquine (65 mg/kg)-elicited seizures. 6. Diazepam (1 mg/kg) and phenobarbitone (20 mg/kg) significantly antagonised chloroquine (65 mg/kg) seizures. The onset of seizures was significantly delayed by both diazepam (0.25-1 mg/kg) and phenobarbitone (10-20 mg/kg). 7. These data suggest that enhancement and inhibition of GABAergic neurotransmission respectively attenuate and potentiate chloroquine seizures in mice.