Dopamine release rather than content in the caudate putamen is associated with behavioral changes in the iron rat model of Parkinson's disease.

The effects of intranigral iron injection on dopamine (DA) release and content in the caudate putamen (CPu) and their relationship to DA-related behavioral response were investigated in rats. Different concentrations of FeCl(3) (10, 20, and 40 microg) and saline were injected separately into the left substantia nigra. In some experiments, rats were pretreated with desferrioxamine or saline before iron injection. After 3 weeks, changes in behavioral response, DA release, and DA content in the CPu were determined. In all iron injection groups (10, 20, and 40 microg), DA content in the lesioned side of the brain was significantly decreased, showing a significant linear correlation (R(2) = 0.981, P = 0.01), and DA turnover ratio significantly increased (both P = 0.01, 0.01 and 0.001 vs unlesioned sides, respectively). However, injection dosages of 10 or 20 microg of iron did not lead to significant changes in DA release in the CPu or in behavioral response. At the 40-microg dosage, it was found that DA release in the lesioned side and rearing activity both were significantly reduced (all P = 0.01 vs unlesioned side or control) and apomorphine-induced rotation was observed. Pretreatment with desferrioxamine significantly inhibited the effect of iron on DA release and content. These results demonstrate that iron injection can damage dopaminergic neurons and suggest that DA release, rather than DA content, in the CPu is associated with DA-related behavioral changes in this PD model.