Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Volkow
N D
ND
Department of Psychiatry, State University of New York at Stony Brook, USA. volkow@bnl.gov
Chang
L
L
Wang
G J
GJ
Fowler
J S
JS
Leonido-Yee
M
M
Franceschi
D
D
Sedler
M J
MJ
Gatley
S J
SJ
Hitzemann
R
R
Ding
Y S
YS
Logan
J
J
Wong
C
C
Miller
E N
EN
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000032:analysis* / Q000187:drug effects* / Q000378:metabolism; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000032:analysis* / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008694:Methamphetamine / Q000009:adverse effects* / Q000378:metabolism / Q000494:pharmacology; D008774:Methylphenidate / Q000378:metabolism; D009419:Nerve Tissue Proteins; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D011596:Psychomotor Disorders / Q000139:chemically induced / Q000175:diagnosis* / Q000378:metabolism; D011699:Putamen / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D019966:Substance-Related Disorders / Q000000981:diagnostic imaging / Q000378:metabolism*; D014055:Tomography, Emission-Computed / Q000706:statistics & numerical data*; D014706:Verbal Learning / Q000187:drug effects
D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D008774:Methylphenidate; D008694:Methamphetamine; D004298:Dopamine