Augmented depression and reduced excitability of the central nervous system (CNS) by cadmium in the rat

Reports indicating that low doses of cadmium caused vasodilation, but that larger quantities elicited a pressor response, apparently mediated by a CNS reflex, prompted an examination of cadmium-induced changes in CNS responsiveness and activity. Rats were injected intraperitoneally with either 2 mg/kg or 4 mg/kg of CdCl2 solution, after which the CNS was either depressed by pentobarbital or excited by strychnine at different dose levels. Cadmium treatment, administered before pentobarbital, decreased the time required for sleep induction and prolonged sleep duration at doses of either 20 mg/kg or 30 mg/kg: at 40 mg/kg only induction was affected and at 60 mg/kg neither was influenced. At a dosage of 60 micrograms/kg, strychnine caused convulsions in all control animals, but in none pretreated with CdCl2. When either 75 or 120 micrograms/kg of strychnine was used, cadmium at either dosage failed to prevent convulsions, although the onset was delayed and duration curtailed. The rapidity with which Cd modified CNS activity indicated that the effect can not depend upon cadmium-induced synthesis of metallothionine, but represents a direct effect of Cd on the CNS. Cadmium treatment did not substantially improve the survival of rats that convulsed when treated with strychnine.