Antagonism of the D2 dopamine receptor enhances tremor but reduces voluntary muscle activation in humans

J.R. Thorstensen, M.G. Tucker, J.J. Kavanagh

Research output: Contribution to journalArticleResearchpeer-review

9 Citations (Scopus)


Neural circuits that comprise the indirect pathway in the basal ganglia have been implicated in tremor genesis, and possibly play a role in the voluntary activation of muscles. However, an absence of in vivo human studies that target striatal D 2 dopamine receptors of the indirect pathway have prevented causal links being made between the D 2 receptor and motor control. Healthy individuals ingested 3 mg of the competitive D 2 antagonist haloperidol in a double-blinded, placebo-controlled, two-way, cross-over study. Two experiments were performed to examine involuntary and voluntary movement. The first experiment (n = 10) assessed time- and frequency-domain measures of force tremor during isometric elbow flexions, and the second experiment (n = 8) examined voluntary activation of the elbow flexors during unfatigued and fatigued maximum contractions. Blockade of the D 2 receptor had no effect on tremor frequency, but increased the amplitude of force variability and 8–12 Hz power during moderate intensity isometric elbow flexions. These findings provide direct evidence that D 2 receptors relate to physiological tremor generation during muscle contractions, whereby the gain of tremor is increased after D 2 antagonism. The ability to voluntarily activate the elbow flexors was compromised under both non-fatigued and fatigued conditions. Consequently, the duration that maximum contractions could be sustained was reduced with D 2 antagonism. These results provide further support that the D 2 receptor has a critical role in skeletal muscle activation, where central fatigue is exacerbated by enhancing activity of the indirect basal ganglia pathway during maximum muscle contractions.

Original languageEnglish
Pages (from-to)343-352
Number of pages10
Publication statusPublished - Oct 2018
Externally publishedYes


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