Analysis of Locomotor Behavior of an Animal Model of RLS Induced by Iron Deficiency Submitted to Pharmacological Treatments and Physical Exercise

Keywords

restless legs syndrome - behavior - sleep - treatments

Introduction: Clinical conditions regarding restless legs syndrome (RLS) have well-characterized pathophysiological conditions in humans and their investigation is also reproducible in experimental models. In this sense, pharmacological and non-pharmacological treatments that investigate genetic aspects, neurophysiological and biochemical alterations that cause alterations in the dopaminergic and glutamatergic systems, as well as alterations in the adenosinergic system, are using the animal model to understand mechanisms. The rodent model for RLS through iron deficiency stands out, reproducing clinical and sleep conditions similar to those of patients such as sleep architecture, increased wakefulness at the end of the day and behavioral changes that mimic RLS-related characteristics.

Aim: To evaluate exploratory and locomotor behavior in an iron-deficient animal model for RLS during different pharmacological treatments and physical exercise.

Methods: The experimental protocol was approved by the Ethics Committee for the Use of Animals (5561–1/2020). Adult male Wistar rats (n = 43) divided into 6 groups: Control; DFe/Control; DFe/DOPA (dopmergenic agonist treatment); DFe/OPI (opioid treatment); DFe/GABA (treatment with α2δ gabapentin ligand); DFe/EF (treatment with physical exercise). In the experimental procedure, with 80 days of life, pharmacological interventions were started, physical exercise lasting 4 weeks. And the behavioral test (Open Field) once a week in parallel with the intervention (9–11am). For statistical analysis, the mixed linear analysis model and the post hoc Bonferroni test were used, p < 0.05.

Results: The dopaminergic treatment group presented an ambulation total with parameters close to the healthy control, in addition, it indicated a significant reduction when compared with the iron deficiency group (p < 0.05). On the other hand, in the opioid group, greater total ambulation was observed when compared with the dopamine and control groups (p < 0.01). The treatment with physical exercise presented a tendency of results close to dopamine and to the control, with better effects than specific pharmacological agents.

Conclusions: Taken together, the findings suggest that dopaminergic agents in the treatment of the animal model of RLS, have beneficial effects and better results when compared with other treatments. It is observed that physical exercise is relevant in improving locomotor behavior.

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

Publication History

Article published online:
15 June 2023