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Brain serotonin transporter in human methamphetamine users

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Abstract

Rationale

Research on methamphetamine (MA) toxicity primarily focuses on the possibility that some of the behavioural problems in human MA users might be caused by damage to brain dopamine neurones. However, animal data also indicate that MA can damage brain serotonin neurones, and it has been suggested that cognitive problems and aggression in MA users might be explained by serotonergic damage. As information on the brain serotonin system in human MA users is fragmentary, our objective was to determine whether protein levels of serotonin transporter (SERT), a key marker of serotonin neurones, are decreased in brain of chronic MA users.

Methods

SERT immunoreactivity was measured using an immunoblotting procedure in autopsied brain of 16 chronic MA users testing positive for the drug in blood and brain and matched controls.

Results

SERT levels were non-significantly decreased (−14% to −33%) in caudate, putamen and thalamus (normal in hippocampus), and, unlike the robust striatal dopamine reduction, there was marked overlap between control and MA user ranges. Concentrations of SERT were significantly decreased (−23% to −39%) in orbitofrontal and occipital cortices (normal in frontopolar and temporal cortices).

Conclusions

Our data suggest that MA might modestly damage brain serotonin neurones and/or inhibit SERT protein expression, with cerebral cortex being more affected than sub-cortical regions. The SERT reduction in orbitofrontal cortex complements other data suggesting involvement of this area in MA-related behaviour. Decreased brain SERT could also be related to the clinical finding that treatment with a selective serotonin re-uptake inhibitor might increase relapse to MA.

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Acknowledgements

This work was supported by the National Institute of Drug Abuse, National Institute of Health grant DA07182 to SJK and by the New Zealand Institute of Environmental Science and Research, Ltd. to PSF.

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Authors and Affiliations

  1. Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada

    Stephen J. Kish, Isabelle Boileau, Li-Jan Chang & Junchao Tong

  2. ESR Institute of Environmental Science and Research, Auckland, New Zealand

    Paul S. Fitzmaurice

  3. Office of the Polk County Medical Examiner, Des Moines, IA, USA

    Gregory A. Schmunk

  4. Division of Neuropathology, London Health Science Center, University of Western Ontario, London, Ontario, Canada

    Lee-Cyn Ang

  5. Movement Disorder Research Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

    Yoshiaki Furukawa

  6. Clark County Office of the Medical Examiner, Vancouver, WA, USA

    Dennis J. Wickham

  7. Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada

    Allan Sherwin

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  1. Stephen J. Kish
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  10. Junchao Tong
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Correspondence to Junchao Tong.

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Kish, S.J., Fitzmaurice, P.S., Boileau, I. et al. Brain serotonin transporter in human methamphetamine users. Psychopharmacology 202, 649–661 (2009). https://doi.org/10.1007/s00213-008-1346-x

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