Brain serotonin transporter in human methamphetamine users.
BACKGROUND
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.
Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada.
Stephen J
SJ
Kish
Paul S
PS
Fitzmaurice
Isabelle
I
Boileau
Gregory A
GA
Schmunk
Lee-Cyn
LC
Ang
Yoshiaki
Y
Furukawa
Li-Jan
LJ
Chang
Dennis J
DJ
Wickham
Allan
A
Sherwin
Junchao
J
Tong
D000328:Adult; D019969:Amphetamine-Related Disorders / Q000378:metabolism*; D001344:Autopsy; D001923:Brain Chemistry / Q000187:drug effects*; D000697:Central Nervous System Stimulants; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005260:Female; D006197:Hair / Q000737:chemistry; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D008694:Methamphetamine; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D055815:Young Adult
D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D008694:Methamphetamine; D006897:Hydroxyindoleacetic Acid; D014365:Tryptophan Hydroxylase; D004298:Dopamine