Persistent cognitive and dopamine transporter deficits in abstinent methamphetamine users

Synapse. 2008 Feb;62(2):91-100. doi: 10.1002/syn.20471.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Amphetamine-Related Disorders / diagnostic imaging
  • Amphetamine-Related Disorders / metabolism*
  • Amphetamine-Related Disorders / physiopathology*
  • Analysis of Variance
  • Cocaine / analogs & derivatives
  • Cocaine / metabolism
  • Cognition / drug effects*
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / drug effects
  • Dopamine / metabolism*
  • Dopamine Uptake Inhibitors / pharmacology*
  • Female
  • Humans
  • Male
  • Methamphetamine / administration & dosage*
  • Middle Aged
  • Neuropsychological Tests
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / diagnostic imaging
  • Parkinson Disease, Secondary / metabolism
  • Parkinson Disease, Secondary / physiopathology
  • Positron-Emission Tomography / methods


  • Dopamine Uptake Inhibitors
  • Methamphetamine
  • (1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester
  • Cocaine
  • Dopamine