L-tyrosine hydroxylase activity in the rat brain after chronic oral administration of manganese chloride.

In rats chronically treated with a high oral load of MnCl2 a significant increase in the activity of L-tyrosine hydroxylase was observed in neostriatum, midbrain and hippocampus one month after the beginning of the experiment. The augmented enzymatic activity persisted in neostriatum, midbrain and hypothalamus on the third month and remained elevated only in neostriatum on the sixth month. After eight months a significant decrease in the activity of the enzyme was found in neostriatum with no changes in the remaining regions studied. These findings are interesting since human manganese intoxication starts with a psychiatric phase bearing similarities to schizophrenia in which the primary disturbance has been suggested to be an overactivity of dopamine neurons. On the contrary, the permanent neurological phase is associated with reduced striatal dopamine, presumably due to a decrease in L-tyrosine hydroxylase activity.