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Effect of various antiepileptic drugs in zebrafish PTZ-seizure model

Author(s): P Gupta1, SB Khobragade2, VM Shingatgeri2
1Central Research Institute for Homoeopathy, Sec-24, Noida-201 301, India 2Drug Safety Evaluation, Ranbaxy Research Laboratories, Sector 18, Gurgaon-122 015, India

Correspondence Address:
P Gupta Central Research Institute for Homoeopathy, Sec-24, Noida-201 301 India E-mail: [email protected]

Recently zebrafish larvae have emerged as a high-throughput model for screening pharmacological activities. The present study was undertaken to investigate the effect of established anticonvulsants, such as valproic acid, carbamazepine, gabapentin, diazepam, lacosamide and pregabalin against pentylenetetrazole (6 mM) seizures in adult zebrafish. Different phases of seizures (increase swim activity, rapid whirlpool-like circling swim behaviour and brief clonus-like seizures leading to loss of posture) were elicited in zebrafish on exposure for 15 min to 6 mM pentylenetetrazole. The exposure of zebrafish to an increasing concentration of the anticonvulsants alongside 6 mM pentylenetetrazole showed concentration-dependent elevation of seizure latency against pentylenetetrazole-induced seizures except for pregabalin, which failed to produce any anticonvulsant activity in zebrafish. Moreover the proconvulsant activity of caffeine was also evaluated using suboptimal concentration (4 mM) of pentylenetetrazole in adult zebrafish. Decrease in seizure latency of different phases of seizures was observed with increasing concentration of caffeine compared with its respective control group. In view of the above findings, the results of the present study suggested that adult zebrafish produce the expected anticonvulsive and proconvulsive effects and could potentially be used as a screen in future epilepsy research.

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