The effects of acute dopamine depletion on resting-state functional connectivity in healthy humans

Fernando Caravaggio, Alexander J. Barnett, Shinichiro Nakajima, Yusuke Iwata, Julia Kim, Carol Borlido, Wanna Mar, Philip Gerretsen, Gary Remington, Ariel Graff-Guerrero

研究成果: Article査読

2 被引用数 (Scopus)


Alpha-methyl-para-tyrosine (AMPT), a competitive inhibitor of tyrosine hydroxylase, can be used to deplete endogenous dopamine in humans. We examined how AMPT-induced dopamine depletion alters resting-state functional connectivity of the basal ganglia, and canonical resting-state networks, in healthy humans. Fourteen healthy participants (8 females; age [mean ± SD] = 27.93 ± 9.86) completed the study. Following dopamine depletion, the caudate showed reduced connectivity with the medial prefrontal cortex (mPFC) (Cohen's d = 1.89, p<.0001). Moreover, the caudate, putamen, globus pallidus, and midbrain all showed reduced connectivity with the occipital cortex (Cohen's d = 1.48–1.90; p<.0001–0.001). Notably, the dorsal caudate showed increased connectivity with the sensorimotor network (Cohen's d = 2.03, p=.002). AMPT significantly decreased self-reported motivation (t(13)=4.19, p=.001) and increased fatigue (t(13)=4.79, p=.0004). A greater increase in fatigue was associated with a greater reduction in connectivity between the substantia nigra and the mPFC (Cohen's d = 3.02, p<.00001), while decreased motivation was correlated with decreased connectivity between the VTA and left sensorimotor cortex (Cohen's d = 2.03, p=.00004). These findings help us to better understand the role of dopamine in basal ganglia function and may help us better understand neuropsychiatric diseases where abnormal dopamine levels are observed.

ジャーナルEuropean Neuropsychopharmacology
出版ステータスPublished - 2022 4月

ASJC Scopus subject areas

  • 薬理学
  • 神経学
  • 臨床神経学
  • 精神医学および精神衛生
  • 生物学的精神医学
  • 薬理学(医学)


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