Psychopharmacology

, Volume 185, Issue 3, pp 327–338

Cognitive function and nigrostriatal markers in abstinent methamphetamine abusers

  • Chris-Ellyn Johanson
  • Kirk A. Frey
  • Leslie H. Lundahl
  • Pamela Keenan
  • Nancy Lockhart
  • John Roll
  • Gantt P. Galloway
  • Robert A. Koeppe
  • Michael R. Kilbourn
  • Trevor Robbins
  • Charles R. Schuster
Original Investigation

DOI: 10.1007/s00213-006-0330-6

Cite this article as:
Johanson, CE., Frey, K.A., Lundahl, L.H. et al. Psychopharmacology (2006) 185: 327. doi:10.1007/s00213-006-0330-6

Abstract

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.

Method

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.

Keywords

Methamphetamine Human Neurocognitive function PET Neuroimaging Dopamine transporter DAT VMAT2 

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Chris-Ellyn Johanson
    • 1
    • 7
  • Kirk A. Frey
    • 2
    • 3
  • Leslie H. Lundahl
    • 1
  • Pamela Keenan
    • 1
  • Nancy Lockhart
    • 1
  • John Roll
    • 4
  • Gantt P. Galloway
    • 5
  • Robert A. Koeppe
    • 2
  • Michael R. Kilbourn
    • 2
  • Trevor Robbins
    • 6
  • Charles R. Schuster
    • 1
  1. 1.Department of Psychiatry and Behavioral NeurosciencesWayne State UniversityDetroitUSA
  2. 2.Department of Radiology, Division of Nuclear MedicineThe University of MichiganAnn ArborUSA
  3. 3.Molecular and Behavioral Neuroscience InstituteThe University of MichiganAnn ArborUSA
  4. 4.Friends Research InstituteLos AngelesUSA
  5. 5.Haight Ashbury Free ClinicsSan FranciscoUSA
  6. 6.Department of PsychologyCambridge UniversityCambridgeUK
  7. 7.Substance Abuse Research Division, Department of Psychiatry and Behavioral NeurosciencesWayne State UniversityDetroitUSA

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