Ketamine blockade of cortical spreading depression in rats.

The failure to elicit cortical spreading depression (SD) under ketamine anesthesia has been examined in 25 rats. SD was elicited by microinjection of K+ acetate (1 microliter, 0.15 mol/l) into the cerebral cortex and monitored by recording the accompanying slow-potential waves. I.p. injection of ketamine HCl (50 mg/kg) elicited after 5-10 min blockade of SD propagation lasting 30-40 min. SD penetration into a cortical area superfused with 10(-4) and 10(-3) mol/l ketamine was partly or completely blocked, respectively. Systemic ketamine doses eliciting SD blockade only slightly reduced spontaneous activity of cortical units recorded with carbon fiber microelectrodes and did not increase but rather decreased the rate of K+ removal from a KCl pool (30 microliters, 40 mmol/l) contacting a 12.5 mm2 area of exposed cortical surface. The results indicate that the ketamine-induced SD blockade is due neither to epileptic activity nor to enhanced active transport of ions but rather to interference with chemically gated ionic channels and/or to stabilization of postsynaptic membranes.