MAGNESIUM-DEFICIENCY INCREASES KETAMINE SENSITIVITY IN RATS

Purpose: Inhibition of the NMDA receptor likely contributes to ketamin e's neurodepressive properties, Magnesium also inhibits the NMDA recep tor by binding to a site associated with the ketamine-binding domain. Electrophysiological studies suggest that magnesium prevents ketamine from binding to the NMDA receptor and thereby prevents ketamine inhibi tion. We undertook an in vivo study to determine if magnesium deficien cy was associated with an increased sensitivity to ketamine. Methods: Weanling rats were maintained on a Mg2+-deficient or control diet for 14 days. In Study I, rats were anaesthetized then sacrificed and the M g2+ concentrations in the brain and plasma were measured. In a second prospective study, experimental animals were rendered hypomagnesaemic and the potency of 125 mg.kg(-1) ip ketamine was evaluated. Animals we re then were fed a Mg2+-containing diet and ketamine sensitivity was r e-examined 14 days later. Results: The Mg2+-deficient diets rendered t he rats hypomagnesaemic as indicated by the brain and plasma concentra tion of Mg2+. In Study 2, the time to loss of righting reflex was shor ter: 1.9 +/- 0.3 min (n = 12) and 2.6 +/- 0.2 min (n = 16, P < 0.05), whereas the latency to toe pinch was prolonged: 25.0 +/- 5.8 min (n = 12) vs 3.1 +/- 2.1 min (n = 16, P < 0.05) in the Mg2+-deficient compar ed with age-matched control animals, respectively. The hypomagnesaemic animals had a higher death rate following ketamine injection. The inc reased sensitivity to ketamine was no longer apparent when the animals were re-tested following replenishment of Mg2+. Conclusion: Hypomagne saemia is associated with an increased sensitivity to ketamine.