Possible mechanism of anticonvulsant effect of ketamine in mice

1002-1008<span style="font-size: 15.0pt;mso-bidi-font-size:8.0pt;font-family:" times="" new="" roman","serif""="">The study was designed to investigate the effect of ketamine on convulsive behaviour using maximal electro shock (MES) test. An attempt was also made to study the possible receptor mechanisms involved. MES seizures were induced in mice <span style="font-size:15.5pt;mso-bidi-font-size:8.5pt;font-family: " times="" new="" roman","serif""="">via <span style="font-size:15.0pt; mso-bidi-font-size:8.0pt;font-family:" times="" new="" roman","serif""="">transauricular electrodes (60mA, 0.2sec). Seizure severity was assessed by the duration of tonic hindlimb extensor phase and mortality due to convulsions. Intraperitoneal administration of ketamine produced a dose-dependent (5-50mg/kg) protection against hindlimb extensor phase. The anticonvulsant effect of ketamine was antagonized neither by naloxone (low as well as high doses) nor sulpiride, but was attenuated by haloperidol, a dopamine (D<span style="font-size:13.0pt;mso-bidi-font-size: 6.0pt;font-family:" times="" new="" roman","serif""="">2)/sigma receptor antagonist. Coadministration of γ-aminobutyric acid (GABA)-ergic drugs (GABA, muscimol, diazepam and baclofen) and N-methyi-D-aspartate (NMDA) receptor antagonist, dizocilpine (MK801) with ketamine facilitated the anticonvulsant action of the latter drug. In contrast, flumazenil, a benzodiazepine (BZD)-GABAA receptor antagonist, reversed the facilitatory effect of diazepam on the anti-MES effect of ketamine. Similarly, δ-aminovaleric acid (DAVA), antagonized the facilitatory effect of baclofen on anti-MES action of ketamine. These BZD-GABAergic antagonists, flumazenil or DAVA per se <span style="font-size:15.0pt;mso-bidi-font-size:8.0pt; font-family:" times="" new="" roman","serif""="">also attenuated the anti-MES effect of ketamine given alone. The results suggest that besides its known antagonistic effect on NMDA channel, other neurotransmitter systems i.e. sigma, GABAA-BZD-chloride channel complex and GABAB<span style="font-size:13.0pt; mso-bidi-font-size:6.0pt;font-family:" times="" new="" roman","serif""=""> receptors may also be involved in the anti-MES action of ketamine.