EFFECTS OF CADMIUM AND VERAPAMIL ON KETAMINE-INDUCED ANESTHESIA IN MICE

Previous studies have shown that pretreatment with cadmium and verapam il potentiated the effects of some CNS active drugs. The objective of this study was to determine the influence of these-agents on ketamine anesthesia in adult male mice. Intraperitoneal administration of 300 m g ketamine/kg produced sleeping time of 40.88 +/- 2.98 min. Pretreatme nt with a single dose of either 3 mg cadmium/kg sc or 5 mg verapamil/k g ip alone significantly increased the duration of sleeping time (40.8 8 +/- 2.98 vs 55.09 +/- 4.20 and 49.01 +/- 3.09 min). Pretreatment wit h cadmium plus verapamil produced significant additive effects on keta mine-induced anesthesia (40.88 +/- 2.98 vs 70.32 +/- 4.64 min). Pretre atment with 3 mg cadmium/kg sc before 1 w caused a reduction in the po tentiating effects of a 2nd dose of cadmium in ketamine-induced anesth esia in mice. These results indicate that prolongation of ketamine-ind uced anesthesia by cadmium and verapamil could be mediated either by i nhibition of hepatic P-450 metabolizing enzymes or neuronal calcium ch annels blockade. The tolerance to the potentiating effects of cadmium could be mediated by hepatic metallothionein induction and a reduction in total body cadmium burden.