A brief history of the neurobehavioral toxicity of manganese: some unanswered questions.

It was observed by Couper in 1837 that manganese dust produces a neurological syndrome characterized by muscle weakness, tremor, bent posture, whispered speech and excess salivation. The similarity of these symptoms to those of Parkinson's disease were not recognized for many years. In addition to its Parkinson-like effects, manganese produces behavioral symptoms in humans including nervousness, hallucinations, memory loss, cognitive problems, bizarre behaviors and flight of ideas. Despite these signs and symptoms, there have been few systematic attempts to study the effects of manganese on behavior using animal models. The need to better understand the effects of manganese on behavior is becoming more important due to the potential of increased environmental exposure to manganese due to its use, or proposed use as a gasoline additive in a number of countries. However, there is debate as to which manganese compounds should receive priority for testing, what route of administration should be used in this testing, what dosing regimens should be used, what species are appropriate for behavioral testing, and what behavioral tests should be selected. Research to answer these questions is needed so that the behavioral effects of manganese can be described comprehensively and the mechanisms underlying these effects can be understood.