Motor hyperactivity of the iron‐deficient rat — an animal model of restless legs syndrome

BACKGROUND: Abnormal striatal dopamine transmission has been hypothesized to cause restless legs syndrome. Dopaminergic drugs are commonly used to treat restless legs syndrome. However, they cause adverse effects with long‐term use. An animal model would allow the systematic testing of potential therapeutic drugs. A high prevalence of restless legs syndrome has been reported in iron‐deficient anemic patients. We hypothesized that the iron‐deficient animal would exhibit signs similar to those in restless legs syndrome patients. METHODS: After baseline polysomnographic recordings, iron‐deficient rats received pramipexole injection. Then, iron‐deficient rats were fed a standard rodent diet, and polysomnographic recording were performed for 2 days each week for 4 weeks. RESULTS: Iron‐deficient rats have low hematocrit levels and show signs of restless legs syndrome: sleep fragmentation and periodic leg movements in wake and in slow‐wave sleep. Iron‐deficient rats had a positive response to pramipexole treatment. After the iron‐deficient rats were fed the standard rodent diet, hematocrit returned to normal levels, and sleep quality improved, with increased average duration of wake and slow‐wave sleep episodes. Periodic leg movements decreased during both waking and sleep. Hematocrit levels positively correlated with the average duration of episodes in wake and in slow‐wave sleep and negatively correlated with periodic leg movements in wake and in sleep. Western blot analysis showed that striatal dopamine transporter levels were higher in iron‐deficient rats. CONCLUSIONS: The iron‐deficient rat is a useful animal model of iron‐deficient anemic restless legs syndrome. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society