MODULATION OF SEIZURE ACTIVITY BY ALCHORNEA LAXIFLORA IN MICE
Chukwunwike Nwonu*, Olapade Ilesanmi and Joseph Agbedahunsi
ABSTRACT
The study investigated the effects of the extracts of Alchornea laxiflora in four models of experimental seizures, the strychnine-, pentylenetetrazole-, picrotoxin-, and the maximal electroshock-induced seizure tests. The rationale was to provide information on the acute toxicity and the anticonvulsant potential of the extracts, as well as the possible involvement of GABAergic and opioidergic pathways in mediating the anticonvulsant effects of the extracts. Mice of both sexes (n=6) weighing 18 – 22 g were used in the study, and were randomised into control and test groups, which summed up to seven (7) groups. The control group (1) received 10 % Tween 80 (vehicle), 0.1 ml/10 g mouse while the test groups (II, III, IV, V, VI) were administered graded doses (100, 200, 400, 800, 1600 mg/kg, p.o.) of the extracts. The standard group (VII) received standard drugs, Diazepam (2 mg/kg, i.p.) and Phenytoin sodium (25 mg/kg, i.p.). In another set of experiments in mice (n=6), a specific dose of the extracts (1600 mg/kg, p.o.) was used to evaluate the involvement of the GABAergic and the opioidergic pathways in the anticonvulsant effects of the plant extracts. Flumazenil (2 mg/kg, i.p.) and Naloxone (5 mg/kg, i.p.) were used in assessing the signalling pathway(s) mediating the anticonvulsant activity of A. laxiflora.The animals were observed for seizure threshold (latency), death threshold, duration of tonic hind limb extension and the seizure recovery time of the animals. They were individually scored and recorded after observation in the observation cage, 30 min post intra-peritoneal and 1 h post oral administrations of vehicle, extracts or drugs. The results showed that the LD50 for the aqueous and methanol extracts of A. laxiflora in the oral route was > 1600 mg/kg respectively, and found to be safe in animals. However, the LD50 (i.p.), was found to be 400 mg/kg for the methanol extract, which was relatively toxic, and > 1600 mg/kg for the aqueous extract. A. laxiflora demonstrated significant (P < 0.05) anticonvulsant activity, by the increase in seizure threshold and death threshold, decrease in the duration of tonic hind limb extension, and the decrease in seizure recovery time of the animals. The study concluded that the extracts of A. laxiflora have anticonvulsant activity in mice. The anticonvulsant effects were found to be mediated neither via the GABAergic nor the opioidergic pathway.
Keywords: convulsion, recovery time, maximal electroshock, pentylenetetrazole, picrotoxin, strychnine.
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