The Effect of Zinc on the Central Nervous System : Increase in Brain Excitability and Initiation of Seizures Following Systemic and Intracerebral Administration of Zinc

1. The effect of zinc on the central nervous system was investigated in conscious mice using electroshock seizure threshold tests and whole animal behavioral studies. 2. Single or successive subcutaneous injection of zinc markedly decreased EST. This EST-lowering effect was abolished in adrenalectomized mice, indicating that the decrease in EST following systemic injection of zinc is produced by way of the adrenal gland. 3. Intracerebral injection of lower concentrations of zinc produced a marked decrease in EST in intact and adrenalectomized mice. 4. Intracerebral injection of higher concentrations of zinc produced the following behavioral changes. A) A concentration of 4 mM or more of zinc (2.6 μg or more Zn per 0.01 ml) produced running or hopping movements, which were followed by convulsive seizures with a latency of about 50 sec. The seizure pattern was almost always tonic flexor-tonic extensor type. B) Such seizure responses seemed to be rather specific for zinc, since copper produced a different type of seizure responses and several heavy metals had little effect on behavior. C) Diphenylhydantoin, phenobarbital and acetazolamide protected the tonic extensor seizures but failed to eliminate the running or hopping movements preceding the seizures. Calcium completely protected the behavioral responses to zinc, while the protective effect of magnesium was insufficient. 5. Possible mechanisms concerning the direct effect of zinc on the brain are discussed."