Animal models of restless legs syndrome

Abstract Restless legs syndrome (RLS) is a common disease with prevalence up to 10% in the general population. It is mostly a subjective condition, making animal models intrinsically difficult. General increased activity (urge to move) and limb movements consistent with periodic limb movements of sleep, seen in most patients with RLS, are currently our best behavioral markers. Our best understanding of human RLS demonstrates reduced central nervous system (CNS) iron stores and dysfunction of dopaminergic systems, which most likely involves the spinal cord. Based upon this knowledge, animal manipulations, including destruction of the A11 diencephalic–spinal tract and iron deprivation, have resulted in animal behavior consistent with RLS. Dopamine receptor type 3 knockout mice also show general increased activity. Pharmacologic blockade of dopamine receptors in rodents has also caused movements resembling periodic limb movements of sleep in older rodents but not in younger animals. More sophisticated animal modeling is needed to facilitate our understanding of RLS.