Drugs and Exercise as Treatment of Restless Legs Syndrome in an Animal Model with Iron Deficiency

Keywords

restless legs syndrome - exercise - treatment

Introduction: Restless legs syndrome (RLS) is a common sleep-related movement disorder. An uncomfortable and overwhelming need characterizes RLS or the urge to move the legs with an unpleasant and sometimes painful sensation. The cause of RLS is not fully understood, but evidence suggests that it is related to low brain iron levels and dopamine regulation. In patients with RLS, positive physiological effects linked to performing exercise were identified as the improvement in the sleep pattern.

Objective: The aim was to verify the effect of different drugs (dopamine (DOPA); opioid (OPI); α2δ gabapentin ligand (GABA)) and exercise (EXE) in the treatment of RLS in an animal model with iron deficiency.

Methods: The study was approved by the Ethics Committee on Animal (5561-1/2020). Wistar rats were randomly distributed into five groups: Control (CTRL); Iron Deficiency (ID); and treatments with DOPA; OPI; GABA and EXE. The experimental design induced the animals to RLS through an iron-restricted diet from the 30th day of life. With 80 days of life, the interventions were started for 4 weeks, and the open field behavioral test was performed before and after the beginning of the interventions (one each week). After euthanasia and tissue collection (striatum and spinal cord), qPCR and expression of proteins referring to PTPRD, DAT, TH, and D2. Molecular data analysis occurred by one-way or two-way ANOVA. Post hoc by Duncan or Bonferroni was used. P<0.05.

Results: The gene expression of the striatum in the DOPA group was different in the targets D2, DAT, and TH, compared to the treated and ID. In Western Blotting, the marrow showed a difference in D2 protein for GABA and DOPA treatments compared to ID. The ambulation behavior differed between CTRL, ID, and OPI. The DOPA treatment presented lower total ambulation compared to the OPI. EXE treatment reduces ambulation and improves symptoms after 28 days (p<0,05). The locomotor parameter improvement was observed in the DOPA. Grooming behavior was reduced in the before and after comparison in the EXE. The DOPA group showed increased striatal gene expression in DAT, TH, and D2 targets. All groups except the ID control showed high TH expression. The EXE group showed DAT expression close to the healthy control group and DOPA.

Conclusion: The results indicated that the drugs DOPA and GABA had a better effect on the treatment. Exercise can be a significant treatment or adjunct in controlling and improving SPI symptoms.

No conflict of interest has been declared by the author(s).

Publication History

Article published online:
16 September 2025