Effect of Withania somnifera Dunal root extract against pentylenetetrazol seizure threshold in mice: possible involvement of GABAergic system.

Withania somnifera (ashwagandha) is a widely used herb in the Ayurvedic system of medicine. The objective of the present study was to elucidate the effect of W. somnifera root extract (Ws) alone or in combination with exogenous gamma-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. Ws (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 Ws (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 W. somnifera against PTZ seizure threshold paradigm involved the GABAAergic modulation.

Pro-convulsant effect of cefazolin sodium against pentylenetetrazol- or picrotoxin-induced convulsions in mice.

Cefazolin injection (3000 mg/kg, i.v.) in mice showed several behavioral excitations such as wild running, jumping, rolling, and finally undergoing severe convulsions followed by death. It's lower doses (500-2000 mg/kg, i.v.) were unable to produce any convulsions or behavioral excitations in mice. However, cefazolin (500 or 1000 mg/kg, i.v.) when administered before different doses of pentylenetetrazol (PTZ; 40 or 60 mg/kg, i.p.) or picrotoxin (PTX; 4 or 8 mg/kg, i.p.), it produced severe tonic-clonic convulsions in mice. The convulsions or behavioral excitations produced by 3000 mg/kg, i.v. cefazolin was also reversed by different doses of diazepam (0.5-2 mg/kg, i.p.) further proving the GABAergic modulatory effect of cefazolin. The results conclude the pro-convulsant action of cefazolin on PTZ- or PTX-induced convulsions, and further confirm the clinical reports.