Cognitive function and nigrostriatal markers in abstinent methamphetamine abusers.
OBJECTIVE
Preclinical investigations have established that methamphetamine (MA) produces long-term changes in dopamine (DA) neurons in the striatum. Human studies have suggested similar effects and correlated motor and cognitive deficits. The present study was designed to further our understanding of changes in brain function in humans that might result from chronic high dose use of MA after at least 3 months of abstinence.


METHODS
Brain function in abstinent users was compared to controls using neuroimaging of monoamine transporters and cognitive assessment. Striatal levels of DA transporter (DAT) and vesicular monoamine transporter type-2 (VMAT2) were determined using [11C]methylphenidate and [11C]dihydrotetrabenazine positron emission tomography, respectively. Cognitive function was evaluated using tests of motor function, memory, learning, attention, and executive function.


RESULTS
Striatal DAT was approximately 15% lower and VMAT2 was 10% lower in MA abusers across striatal subregions. The MA abusers performed within the normal range but performed more poorly compared to controls on three of the 12 tasks.


CONCLUSIONS
Failure to find more substantial changes in transporter levels and neurocognitive function may be attributed to the length of time that MA users were abstinent (ranging from 3 months to more than 10 years, mean 3 years), although there were no correlations with length of abstinence. Persistent VMAT2 reductions support the animal literature indicating a toxic effect of MA on nigrostriatal nerve terminals. However, the magnitude of the MA effects on nigrostriatal projection integrity is sufficiently small that it is questionable whether clinical signs of DA deficiency are likely to develop.
Johanson
Chris-Ellyn
CE
Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, MI 48207, USA. cjohans@med.wayne.edu
Frey
Kirk A
KA
Lundahl
Leslie H
LH
Keenan
Pamela
P
Lockhart
Nancy
N
Roll
John
J
Galloway
Gantt P
GP
Koeppe
Robert A
RA
Kilbourn
Michael R
MR
Robbins
Trevor
T
Schuster
Charles R
CR
D000293:Adolescent; D000328:Adult; D019969:Amphetamine-Related Disorders / Q000378:metabolism / Q000503:physiopathology*; D003071:Cognition / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D011581:Psychological Tests; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism
D050483:Dopamine Plasma Membrane Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D008694:Methamphetamine; D004298:Dopamine