Intranigral Iron Injection Induces Behavioral and Biochemical “Parkinsonism” in Rats

Abstract

Elevated iron concentrations in the substantia nigra (SN) pars compacta have been implicated in the development of idiopathic Parkinson's disease. Because, as a transitional metal, iron promotes free radical formation, the role of iron in the degeneration of the nigrostriatal dopamine neurons in Parkinson's disease has received much attention. This study further investigates the cytotoxic effects of iron in the SN. Various concentrations of FeCl 3 (1, 5, and 50 μg of Fe 3+ in 5 μl) were unilaterally injected into the SN of adult rats. The two lower doses of iron had no effect on striatal dopamine levels or on the behavioral responses of the rats. However, injection of 50 μg of Fe 3+ resulted in a substantial selective decrease of striaial dopamine (95%), 3,4‐dihydroxyphenylacetic acid (82%), and homo‐vanillic acid (45%), without any change in norepinephrine concentration. Dopamine‐related behavioral responses, such as spontaneous movements in a novel space and rearing, were significantly impaired, whereas amphetamine administration induced ipsilatcral rotation in the iron‐treated rats. The present study indicates that the nigrostriatal dopamine neurons are susceptible to the presence of ionic iron and thus supports the assumption that iron initiates dopaminergic neu‐rodegeneration in Parkinson's disease.