The effect of clonidine and yohimbine on audiogenic seizures (AGS) in rats

Clonidine in high doses (0.5,1.0 mg/kg) significantly increased the latency for audiogenic seizures (AGS) in rats and reduced seizure severity. At a dose (0.05 mg/kg) which acts more specifically on presynaptic alpha 2-receptors, clonidine did not affect seizure latency, but showed a slight proconvulsant action. Yohimbine tended to decrease seizure-latency at all doses, but statistical significance (p less than 0.05) was only reached at 10 mg/kg. Smaller doses of yohimbine (0.5 and 1.0 mg/kg) showed a proconvulsant effect, while a high dose (10 mg/kg) markedly reduced the severity of AGS. The effect of clonidine on seizure-latency was only antagonized by high-dose yohimbine (10 mg/kg), the combination of these drugs being of marked anticonvulsant efficacy. From these results it can be concluded that the anticonvulsant effect of clonidine does not seem to be mediated through presynaptic alpha 2-receptors. Action on other central noradrenergic receptors, and influences on other transmitters must be taken into account when interpreting the effect of clonidine and yohimbine on AGS in rats.