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Cognitive function and nigrostriatal markers in abstinent methamphetamine abusers

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An Erratum to this article was published on 11 May 2006

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.

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Acknowledgements

This research was supported by Joe Young, Sr funds from the State of Michigan, grants from NIDA (DA12458 to CRS, DA14392 to JR, and R01 DA10641 to GPG), NCRR (RR00042 to KF), and NINDS (NS15655 to KF). PK is presently employed in the medical affair division of Ortho-McNeill/Janssen. TWR consults for Cambridge Cognition. The authors wish to thank staff from Wayne State University (staff of the Neuropsychiatric Research Unit: Ken Bates for recruitment; Ja’Near Mathis for urine analyses; and Cheryl Aubie, Kelty Berardi, and Jennifer Raiter for psychiatric diagnoses, neurocognitive assessments, and data management) and staff from the University of Michigan PET Center.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit, MI, USA

    Chris-Ellyn Johanson, Leslie H. Lundahl, Pamela Keenan, Nancy Lockhart & Charles R. Schuster

  2. Department of Radiology, Division of Nuclear Medicine, The University of Michigan, Ann Arbor, MI, USA

    Kirk A. Frey, Robert A. Koeppe & Michael R. Kilbourn

  3. Molecular and Behavioral Neuroscience Institute, The University of Michigan, Ann Arbor, MI, USA

    Kirk A. Frey

  4. Friends Research Institute, Los Angeles, CA, USA

    John Roll

  5. Haight Ashbury Free Clinics, San Francisco, CA, USA

    Gantt P. Galloway

  6. Department of Psychology, Cambridge University, Cambridge, UK

    Trevor Robbins

  7. Substance Abuse Research Division, Department of Psychiatry and Behavioral Neurosciences, Wayne State University, 2761 E. Jefferson Ave., Detroit, MI, 48207, USA

    Chris-Ellyn Johanson

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  1. Chris-Ellyn Johanson
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Correspondence to Chris-Ellyn Johanson.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s00213-006-0393-4

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Johanson, CE., Frey, K.A., Lundahl, L.H. et al. Cognitive function and nigrostriatal markers in abstinent methamphetamine abusers. Psychopharmacology 185, 327–338 (2006). https://doi.org/10.1007/s00213-006-0330-6

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  • DOI: https://doi.org/10.1007/s00213-006-0330-6

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