The multiple effects of ketamine on the electroencephalographic activity in wag/rij rats

Abstract

Item does not contain fulltextThe effects of ketamine, a non-competitive antagonist at the NMDA receptor, were studied on the EEG in a genetic animal model of generalized absence epilepsy - the WAG/Rij rat strain. Animals of this strain display spontaneous occurring generalized spike-wave discharges (SWDs) in EEG. Ketamine was administered i.p., in a dose of 3, 6, 15 and 30 mg/kg. Biphasic effects of ketamine were observed. The first phase was a dose-dependent suppression of SWDs, followed by a second phase characterized by the facilitation of SWDs. This increase of the discharges was expressed first as an increased number of SWDs, and later on as a significant prolongation of individual discharges. An obvious amplitude modulation of the discharges in this period was also found. During the period of suppression of spike-wave activity, a new phenomenon was observed: quasi-periodic groups of spikes or wave-spikes, with an internal frequency of 4 - 5 Hz and a periodicity of about 5 seconds. That quasi-periodic activity vanished few minutes prior to the recovery of the classical SWDs. However, a specific 5 second amplitude modulation of SWDs remained also in the recovery period. The propensity of that specific ketamine-induced activity was found to be correlated with propensity of SWDs in background EEGs of drug-free animals. It can be concluded that ketamine has more effects on the EEG than previously assumed which cannot be explained by a simple blockade of the NMDA receptor. It is also thought that the obtained specific dynamics of SWDs' frequency may be caused by changes in the activity of the thalamo-cortical pacemaker that is generating SWD