Targeting Dopamine Therapy in RLS

Restless Legs Syndrome

Neurons in the brain require blood and oxygen for proper function. The term neurovascular coupling has been postulated in the 19th century by Roy & Sherrington referring to increased blood flow to active neurons. The rationale of this research relies on the neurovascular coupling, suggesting that increased blood flow to active regions on the brain should supply not only more blood, but also more of a pharmacological agent present in the blood system at the time. Thus, active regions should be affected by the agent (=drug) to a greater extent. In the present study we focus on the dopaminergic system, critical in many functions such as cognition, response to stimuli and movement. One of the well-known dopaminergic pathways in the brain is the nigrostriatal pathway, mediating motor function. In this research, we intend to examine the effects of coupling functional activation in this pathway with a dopaminergic agent, Carbidopa/Levodopa, on symptoms of Restless Leg Syndrome (RLS). RLS is characterized by an irresistible urge to move the limbs (i.e. Akathisia), and results most prominently by a significant decrease in the quality of sleep. Our research focuses on this symptom of RLS to examine the effect of coupling brain activation and drug treatment. The first line of treatment in RLS is dopaminergic drugs. These drugs increase dopamine levels in motor pathways, and our research will aim to couple activation in the nigrostriatal motor pathway with dopaminergic treatment in RLS. Functional activation will be achieved with a simple motor task, known to elicit activation in the nigrostriatal pathway. We hypothesize that the drug will act upon the pre-activated motor system, and that this coupling between brain activation and drug treatment will ameliorate sleep-related symptoms of RLS, compared with treating these symptoms solely with a dopaminergic drug and compared with using a non-motor task.

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