Abstract
Restless Legs Syndrome (RLS) is a dopamine-dependent disorder characterized by a strong urge to move. The objective of this study was to evalulate blood levels of dopamine and other catecholamines and blood D2-subtype dopamine receptors (D2Rs) in RLS. Dopamine levels in blood samples from age-matched unmedicated RLS subjects, medicated RLS subjects and Controls were evaluated with high performance liquid chromatography and dopamine D2R white blood cell (WBC) expression levels were determined with fluorescence-activated cell sorting and immunocytochemistry. Blood plasma dopamine levels, but not norepinepherine or epinephrine levels, were significantly increased in medicated RLS subjects vs unmedicated RLS subjects and Controls. The percentage of lymphocytes and monocytes expressing D2Rs differed between Control, RLS medicated and RLS unmedicated subjects. Total D2R expression in lymphocytes, but not monocytes, differed between Control, RLS medicated and RLS unmedicated subjects. D2Rs in lymphocytes, but not monocytes, were sensitive to dopamine in Controls only. Downregulation of WBCs D2Rs occurs in RLS. This downregulation is not reversed by medication, although commonly used RLS medications increase plasma dopamine levels. The insensitivity of monocytes to dopamine levels, but their downregulation in RLS, may reflect their utility as a biomarker for RLS and perhaps brain dopamine homeostasis.
Highlights
The strong urge to move is the most characteristic feature of Restless Legs Syndrome (RLS)/Willis– Ekbom Disease (WED) [1]
D2-subtype dopamine receptors were expressed in both lymphocytes and monocytes in both RLS and control subjects (Figure 2)
The % cells expressing D2 receptors (D2Rs) and the total expression of D2Rs/cell was significantly greater in monocytes than lymphocytes [% cells: 49.6 ± 5.0 vs 13.3 ± 1.5; Figure 1 | Enhanced dopamine levels in restless legs syndrome (RLS) medicated subjects. (A) Blood plasma norepinepherine (NE) levels were the highest of all the catecholamines, but did not differ between Control and RLS medicated and unmedicated subjects. (B) Epinepherine (EPI) levels likewise did not differ between Control and RLS medicated and unmedicated subjects. (C) Dopamine (DA) levels were significantly greater in RLS medicated subjects than in Controls
Summary
The strong urge to move is the most characteristic feature of Restless Legs Syndrome (RLS)/Willis– Ekbom Disease (WED) [1]. The most compelling theory involves the neurotransmitter dopamine (DA) [3], the hypofunctioning in brain DA signaling [4]. Supporting evidence for this notion is given by the fact that RLS symptoms decrease with drugs that stimulate the DA system and are produced with drugs that block DA neurotransmission in the brain [5]. The levels of DA in the brain are directly proportional to the number of brain DA D2 receptors (D2Rs) [6, 7], which are autoreceptors on DA neurons in the midbrain nigrostriatal
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