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

Abstract

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.

• Authors: Esteban A Fridman, Joseph R Osborne, Paul D Mozley, Jonathan D Victor, Nicholas D Schiff
• Journal: Brain : a journal of neurology (Brain) Vol. 142 Issue 7 Pg. 1887-1893 (07 01 2019) ISSN: 1460-2156 [Electronic] England
• PMID: 31505542 (Publication Type: Controlled Clinical Trial, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: [email protected].

Chemical References

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

Topics

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