Extrapyramidal system neurotoxicity: animal models

The central nervous system's extrapyramidal system provides involuntary motor control to the muscles of the head, neck, and limbs. Toxicants that affect the extrapyramidal system are generally clinically characterized by impaired motor control, which is usually the result of basal ganglionic dysfunction. A variety of extrapyramidal syndromes are recognized in humans and include Parkinson's disease, secondary parkinsonism, other degenerative diseases of the basal ganglia, and clinical syndromes that result in dystonia, dyskinesia, essential tremor, and other forms of tremor and chorea. This chapter briefly reviews the anatomy of the extrapyramidal system and discusses several naturally occurring and experimental models that target the mammalian (nonhuman) extrapyramidal system. Topics discussed include extrapyramidal syndromes associated with antipsychotic drugs, carbon monoxide, reserpine, cyanide, rotenone, paraquat, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and manganese. In most cases, animals are used as experimental models to improve our understanding of the toxicity and pathogenesis of these agents. Another agent discussed in this chapter, yellowstar thistle poisoning in horses, however, represents an important spontaneous cause of parkinsonism that naturally occurs in animals. The central focus of the chapter is on animal models, especially the concordance between clinical signs, neurochemical changes, and neuropathology between animals and people.