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The Journal of Neuroscience, October 15, 1998, 18(20):8417-8422
Reduced Striatal Dopamine Transporter Density in Abstinent
Methamphetamine and Methcathinone Users: Evidence from Positron
Emission Tomography Studies with [11C]WIN-35,428
Una D.
McCann1,
Dean F.
Wong2,
Fuji
Yokoi2,
Victor
Villemagne2,
Robert F.
Dannals2, and
George A.
Ricaurte3
1 Unit on Anxiety Disorders, Biological Psychiatry
Branch, National Institute of Mental Health, Intramural Research
Program, Bethesda, Maryland 20892, and 2 Department of
Radiology, Division of Nuclear Medicine and
3 Department of Neurology, The Johns Hopkins Medical
Institutions, Baltimore, Maryland 21224
Methamphetamine and methcathinone are psychostimulant drugs with
high potential for abuse. In animals, methamphetamine and related drugs
are known to damage brain dopamine (DA) neurons, and this damage has
recently been shown to be detectable in living nonhuman primates by
means of positron emission tomography (PET) with
[11C]WIN-35,428, a DA transporter (DAT) ligand.
The present studies determined whether living humans with a history of
methamphetamine or methcathinone abuse showed evidence of lasting
decrements in brain DAT density. PET studies were performed in 10 control subjects, six abstinent methamphetamine users, four abstinent
methcathinone users, and three patients with Parkinson's disease (PD).
On average, subjects had abstained from amphetamine use for ~3 years.
Before PET studies, all subjects underwent urine and blood toxicology screens to rule out recent drug use. Compared with controls, abstinent methamphetamine and methcathinone users had significant decreases in
DAT density in the caudate nucleus ( 23 and 24%, respectively) and
putamen (25 and 16%, respectively). Larger decreases in DAT
density were evident in patients with PD (47 and 68% in caudate and
putamen, respectively). Neither methamphetamine nor methcathinone users
showed clinical signs of parkinsonism. Persistent reductions of DAT
density in methamphetamine and methcathinone users are suggestive of
loss of DAT or loss of DA terminals and raise the possibility that as
these individuals age, they may be at increased risk for the
development of parkinsonism or neuropsychiatric conditions in which
brain DA neurons have been implicated.
Key words:
amphetamines; methamphetamine; dopamine; neurotoxicity; dopamine transporter; parkinsonism
Copyright © 1998 Society for Neuroscience 0270-6474/98/18208417-06$05.00/0
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