Evidence for Dopamine Abnormalities in the Substantia Nigra in Cocaine Addiction Revealed by Neuromelanin-Sensitive MRI

Am J Psychiatry. 2020 Nov 1;177(11):1038-1047. doi: 10.1176/appi.ajp.2020.20010090. Epub 2020 Aug 28.

Abstract

Objective: Recent evidence supports the use of neuromelanin-sensitive MRI (NM-MRI) as a novel tool to investigate dopamine function in the human brain. The authors investigated the NM-MRI signal in individuals with cocaine use disorder, compared with age- and sex-matched control subjects, based on previous imaging studies showing that this disorder is associated with blunted presynaptic striatal dopamine.

Methods: NM-MRI and T1-weighted images were acquired from 20 participants with cocaine use disorder and 35 control subjects. Diagnostic group effects in NM-MRI signal were determined using a voxelwise analysis within the substantia nigra. A subset of 20 cocaine users and 17 control subjects also underwent functional MRI imaging using the monetary incentive delay task, in order to investigate whether NM-MRI signal was associated with alterations in reward processing.

Results: Compared with control subjects, cocaine users showed significantly increased NM-MRI signal in ventrolateral regions of the substantia nigra (area under the receiver operating characteristic curve=0.83). Exploratory analyses did not find a significant correlation of NM-MRI signal to activation of the ventral striatum during anticipation of monetary reward.

Conclusions: Given that previous imaging studies show decreased dopamine signaling in the striatum, the finding of increased NM-MRI signal in the substantia nigra provides additional insight into the pathophysiology of cocaine use disorder. One interpretation is that cocaine use disorder is associated with a redistribution of dopamine between cytosolic and vesicular pools, leading to increased accumulation of neuromelanin. The study findings thus suggest that NM-MRI can serve as a practical imaging tool for interrogating the dopamine system in addiction.

Keywords: Cocaine Use Disorder; Dopamine; Neuromelanin-Sensitive MRI; Substantia Nigra.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anticipation, Psychological
  • Case-Control Studies
  • Cocaine-Related Disorders / diagnostic imaging
  • Cocaine-Related Disorders / metabolism
  • Cocaine-Related Disorders / pathology*
  • Dopamine / metabolism*
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / pathology
  • Female
  • Humans
  • Male
  • Melanins / metabolism*
  • Middle Aged
  • Neuroimaging / methods*
  • Reward
  • Substantia Nigra / diagnostic imaging
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology*
  • Ventral Striatum / metabolism
  • Ventral Striatum / pathology

Substances

  • Melanins
  • neuromelanin
  • Dopamine