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

NEUROPHARMACOLOGY

卷:141

Article

Thorstensen, Jacob R.¹  Tucker, Murray G.²  Kavanagh, Justin J.¹ 

[1] Griffith Univ, Menzies Hlth Inst Queensland, Gold Coast Campus, Gold Coast, Qld, Australia

[2] Univ Hosp Geelong, Barwon Hlth, Mental Hlth Drugs & Alcohol Serv, Geelong, Vic, Australia

关键词: Dopaminergic system;    Maximum voluntary contraction;    Steadiness;    Twitch interpolation;    Central fatigue;   

DOI  :  10.1016/j.neuropharm.2018.08.029

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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