Relationship between the dose-response effects of diazepam and clobazam on electroencephalographic parameters and on kindled amygdaloid seizure activity in rats.
1. The possibility that the anticonvulsant activity of the benzodiazepines, diazepam and clobazam, is related to changes in EEG parameters, particularly beta activity, was investigated in amygdaloid kindled rats. 2. The effects of diazepam (1, 2, 4, 8 and 16 mumols/kg), administered intraperitoneally (i.p.), clobazam (1, 2, 4, 8, 16 and 32 mumols/kg, i.p.) or vehicle (dimethyl sulfoxide) on the cortical EEG of amygdaloid kindled rats were quantitated for 15 min using computerized period amplitude analysis. Immediately afterwards, the amygdala was stimulated and the after-discharge duration (AD) and the seizures stage (SS) were determined. 3. The equivalent percentage time (EPT) of the diazepam-treated group was decreased in the theta band (4-8 Hz) and increased in the alpha (8-12 Hz) and first six beta (12-36 Hz) bands. The mean peak amplitude (MPA) was increased in the alpha (8-12 Hz) and all seven beta bands (12-40 Hz). Clobazam increased the EPT and MPA in the alpha (8-12 Hz) and all seven beta (12-40 Hz) bands. The MPA was also increased by clobazam in the theta (4-8 Hz) band. 4. Diazepam reduced both the AD and SS of the kindled seizures at doses of 4, 8 and 16 mumols/kg, whereas clobazam was anticonvulsant at doses of 16 and 32 mumols/kg. The reduction in both AD and SS correlated with increases in the EPT and MPA in the first beta (12-16 Hz) band in the diazepam-treated group and in the first four beta (12-28 Hz) bands in the clobazam-treated group.
Harris
Q L
QL
University of Melbourne, Austin General Hospital, Heidelberg, Victoria, Australia.
Lewis
S J
SJ
Young
N A
NA
Vajda
F J
FJ
Jarrott
B
B
D000679:Amygdala; D000818:Animals; D014151:Anti-Anxiety Agents; D000927:Anticonvulsants / Q000494:pharmacology*; D001569:Benzodiazepines; D001570:Benzodiazepinones / Q000494:pharmacology*; D000078306:Clobazam; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects*; D007696:Kindling, Neurologic; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012032:Refractory Period, Electrophysiological / Q000187:drug effects
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D001570:Benzodiazepinones; D001569:Benzodiazepines; D000078306:Clobazam; D003975:Diazepam