Persistent cognitive and dopamine transporter deficits in abstinent methamphetamine users.
BACKGROUND
Studies in abstinent methamphetamine (METH) users have demonstrated reductions in brain dopamine transporter (DAT) binding potential (BP), as well as cognitive and motor deficits, but it is not yet clear whether cognitive deficits and brain DAT reductions fully reverse with sustained abstinence, or whether behavioral deficits in METH users are related to dopamine (DA) deficits. This study was conducted to further investigate potential persistent psychomotor deficits secondary to METH abuse, and their relationship to brain DAT availability, as measured using quantitative PET methods with [(11)C]WIN 35428.


METHODS
Twenty-two abstinent METH users and 17 healthy non-METH using controls underwent psychometric testing to test the hypothesis that METH users would demonstrate selective deficits in neuropsychiatric domains known to involve DA neurons (e.g., working memory, executive function, motor function). A subset of subjects also underwent PET scanning with [(11)C]WIN 35428.


RESULTS
METH users were found to have modest deficits in short-term memory, executive function, and manual dexterity. Exploratory correlational analyses revealed that deficits in memory, but not those in executive or motor function, were associated with decreases in striatal DAT BP.


CONCLUSIONS
These results suggest a possible relationship between DAT BP and memory deficits in abstinent METH users, and lend support to the notion that METH produces lasting effects on central DA neurons in humans. As METH can also produce toxic effects on serotonin (5-HT) neurons, further study is needed to address the potential role of brain 5-HT depletion in cognitive deficits in abstinent METH users.
McCann
Una D
UD
Department of Psychiatry, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA. umccann@jhmi.edu
Kuwabara
Hiroto
H
Kumar
Anil
A
Palermo
Michael
M
Abbey
Rubyna
R
Brasic
James
J
Ye
Weiguo
W
Alexander
Mohab
M
Dannals
Robert F
RF
Wong
Dean F
DF
Ricaurte
George A
GA
D000328:Adult; D019969:Amphetamine-Related Disorders / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology*; D000704:Analysis of Variance; D003042:Cocaine / Q000031:analogs & derivatives / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D008875:Middle Aged; D009483:Neuropsychological Tests; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D049268:Positron-Emission Tomography / Q000379:methods
D018765:Dopamine Uptake Inhibitors; D008694:Methamphetamine; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D003042:Cocaine; D004298:Dopamine