Effect of <i style="">Withania somnifera</i> Dunal root extract against pentylenetetrazol seizure threshold in mice: Possible involvement of GABAergic system

Abstract

<i style="">Withania somnifera</i> (ashwagandha) is a widely used herb in the Ayurvedic system of medicine. The objective of the present study was to elucidate the effect of <i style="">W. somnifera</i> root extract (<i style="">Ws</i>) alone or in combination with exogenous g-amino butyric acid (GABA), a GABA receptor agonist or with diazepam, a GABA receptor modulator against pentylenetetrazol (PTZ, iv) seizure threshold in mice. Minimal dose of PTZ (iv, mg/kg) needed to induce different phases (myoclonic jerks, generalized clonus and tonic extension) of convulsions were recorded as an index of seizure threshold. <i style="">Ws </i>(100 or 200 mg/kg, po) increased the PTZ seizure threshold for the onset of tonic extension phase whereas a lower dose (50 mg/kg, po) did not show any effect on the seizure threshold. Co-administration of a sub-effective dose of <i style="">Ws </i>(50 mg/kg, po) with a sub-protective dose of either GABA (25 mg/kg, ip) or diazepam (0.5 mg/kg, ip) increased the seizure threshold. The results suggested that the anticonvulsant effect of <i style="">W. somnifera </i>against PTZ seizure threshold paradigm involved the GABA_Aergic modulation.