Presynaptic dopamine deficit in minimally conscious state patients following traumatic brain injury

Brain. 2019 Jul 1;142(7):1887-1893. doi: 10.1093/brain/awz118.


Dopaminergic stimulation has been proposed as a treatment strategy for post-traumatic brain injured patients in minimally conscious state based on a clinical trial using amantadine, a weak dopamine transporter blocker. However, a specific contribution of dopaminergic neuromodulation in minimally conscious state is undemonstrated. In a phase 0 clinical trial, we evaluated 13 normal volunteers and seven post-traumatic minimally conscious state patients using 11C-raclopride PET to estimate dopamine 2-like receptors occupancy in the striatum and central thalamus before and after dopamine transporter blockade with dextroamphetamine. If a presynaptic deficit was observed, a third and a fourth 11C-raclopride PET were acquired to evaluate changes in dopamine release induced by l-DOPA and l-DOPA+dextroamphetamine. Permutation analysis showed a significant reduction of dopamine release in patients, demonstrating a presynaptic deficit in the striatum and central thalamus that could not be reversed by blocking the dopamine transporter. However, administration of the dopamine precursor l-DOPA reversed the presynaptic deficit by restoring the biosynthesis of dopamine from both ventral tegmentum and substantia nigra. The advantages of alternative pharmacodynamic approaches in post-traumatic minimally conscious state patients should be tested in clinical trials, as patients currently refractory to amantadine might benefit from them.

Keywords: 11C-raclopride; basal ganglia; central thalamus; dopamine 2-like receptors; minimally conscious state.

Publication types

  • Controlled Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Brain Injuries, Traumatic / complications
  • Brain Injuries, Traumatic / metabolism*
  • Corpus Striatum / metabolism
  • Dextroamphetamine / pharmacology
  • Dopamine / deficiency*
  • Dopamine / metabolism*
  • Dopamine Plasma Membrane Transport Proteins / antagonists & inhibitors
  • Female
  • Humans
  • Levodopa / pharmacology
  • Male
  • Persistent Vegetative State / complications
  • Persistent Vegetative State / metabolism*
  • Positron-Emission Tomography
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism*
  • Raclopride / metabolism
  • Receptors, Dopamine D2 / metabolism
  • Substantia Nigra / metabolism
  • Tegmentum Mesencephali / metabolism
  • Thalamus / metabolism
  • Young Adult


  • Dopamine Plasma Membrane Transport Proteins
  • Receptors, Dopamine D2
  • Raclopride
  • Levodopa
  • Dextroamphetamine
  • Dopamine