Ropinirole, a dopamine agonist with high D₃ affinity, reduces proactive inhibition: a double-blind, placebo-controlled study in healthy adults

Abstract

Response inhibition describes the cognitive processes mediating the suppression of unwanted actions. A network involving the basal ganglia mediates two forms of response inhibition: reactive and proactive inhibition. Reactive inhibition serves to abruptly stop motor activity, whereas proactive inhibition is goal-orientated and results in slowing of motor activity in anticipation of stopping. Due to its impairment in several psychiatric disorders, the neurochemistry of response inhibition has become of recent interest. Dopamine has been posed as a candidate mediator of response inhibition due to its role in functioning of the basal ganglia and the observation that patients with Parkinson's disease on dopamine agonists develop impulse control disorders. Although the effects of dopamine on reactive inhibition have been studied, substantial literature on the role of dopamine on proactive inhibition is lacking. To fill this gap, we devised a double-blind, placebo-controlled study of 1 mg ropinirole (a dopamine agonist) on response inhibition in healthy volunteers. We found that whilst reactive inhibition was unchanged, proactive inhibition was impaired when participants were on ropinirole relative to when on placebo. To investigate how ropinirole mediated this effect on proactive inhibition, we used hierarchical drift-diffusion modelling.We found that ropinirole impaired the ability to raise the decision threshold when proactive inhibition was called upon. Our results provide novel evidence that an acute dose of ropinirole selectively reduces proactive inhibition in healthy participants. These results may help explain how ropinirole induces impulse control disorders in susceptible patients with Parkinson's disease.