P20 Antagonism of the D2 dopamine receptor reduces voluntary muscle activation and enhances central fatigue in humans
Thorstensen JT[1], Tucker MG[2] and Kavanagh JJ[1].
- Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia.
- Mental Health, Drugs and Alcohol Service, Barwon Health, University Hospital Geelong, Geelong, Victoria, Australia.
Dysfunction of the dopaminergic system in the basal ganglia has been implicated in motor impairments such as Parkinson’s disease and the neuroleptic-associated tardive dyskinesia. However, an absence of (in vivo) human studies that modulate dopamine receptor activity has clouded the relationship between motor control impairments and dopamine receptor activity. Given that a D2 receptor antagonism suppresses locomotion (1, 2), and the destruction of nigrostriatal dopamine neurons reduces time to exhaustion in animal studies (3, 4), we hypothesised that D2 antagonism would reduce the capacity to voluntarily activate skeletal muscle in humans during fatiguing contractions.
Eight healthy individuals (22.5 ± 1.8 years, 2 females) ingested the D2 antagonist haloperidol in a double-blind, placebo-controlled, two-way, cross-over study. Superimposed and resting twitches were obtained from the elbow flexors before, and after, sustained maximal effort contractions. Level of voluntary activation was calculated from twitch data. Ratings of perceived exertion were collected throughout testing.
The ability to voluntarily activate the elbow flexors to produce a maximal torque was compromised following the blockade of the D2 receptor. This reduction in activation occurred for both unfatigued and fatigued muscle contractions, whereby the D2 antagonism also shortened time-to-fatigue when performing sustained muscle contractions. Ratings of perceived exertion measured during the maximal effort contractions were not affected by D2 antagonism.
This is the first study to provide direct evidence that the D2 receptor has a role in central fatigue, where voluntary muscle activation is reduced with augmented activity in the indirect pathway of the basal ganglia.
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