Association of Dopamine Transporter Reduction With Psychomotor Impairment in Methamphetamine Abusers

TLDR

Methamphetamine is a popular and highly addictive drug that has been shown in laboratory animals to be neurotoxic to dopamine terminals. The study aimed to determine whether methamphetamine use in humans leads to dopamine transporter reductions and whether such reductions have functional consequences. The authors measured dopamine transporter levels using PET scans with [(11)C]d‑threo‑methylphenidate in 15 detoxified methamphetamine abusers and 18 controls, and administered neuropsychological tests to evaluate motor and cognitive function. Methamphetamine abusers exhibited a 27.8 % reduction in caudate and 21.1 % in putamen dopamine transporter levels, which correlated with motor slowing and memory impairment, underscoring the long‑term neurotoxic impact of the drug.

Abstract

Methamphetamine is a popular and highly addictive drug of abuse that has raised concerns because it has been shown in laboratory animals to be neurotoxic to dopamine terminals. The authors evaluated if similar changes occur in humans and assessed if they were functionally significant.Positron emission tomography scans following administration of [(11)C]d-threo-methylphenidate (a dopamine transporter ligand) measured dopamine transporter levels (a marker of dopamine cell terminals) in the brains of 15 detoxified methamphetamine abusers and 18 comparison subjects. Neuropsychological tests were also performed to assess motor and cognitive function.Methamphetamine abusers showed significant dopamine transporter reduction in the striatum (mean differences of 27.8% in the caudate and 21.1% in the putamen) relative to the comparison subjects; this reduction was evident even in abusers who had been detoxified for at least 11 months. Dopamine transporter reduction was associated with motor slowing and memory impairment.These results provide evidence that methamphetamine at dose levels taken by human abusers of the drug leads to dopamine transporter reduction that is associated with motor and cognitive impairment. These results emphasize the urgency of alerting clinicians and the public of the long-term changes that methamphetamine can induce in the human brain.