Serotonin transporter protein in autopsied brain of chronic users of cocaine
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ORIGINAL INVESTIGATION
Serotonin transporter protein in autopsied brain of chronic users of cocaine Junchao Tong 1,2 & Jeffrey H. Meyer 3 & Isabelle Boileau 4 & Lee-Cyn Ang 5 & Paul J. Fletcher 6 & Yoshiaki Furukawa 7 & Stephen J. Kish 2,3 Received: 3 February 2020 / Accepted: 18 May 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Rationale The long-held speculation that the brain serotonin system mediates some behavioral effects of the psychostimulant cocaine is supported in part by the high affinity of cocaine for the serotonin transporter (SERT) and by reports that the serotonin transporter (SERT), estimated by SERT binding, is increased in brain of human chronic cocaine users. Excessive SERT activity and consequent synaptic serotonin deficiency might cause a behavioral (e.g., mood) abnormality in chronic users of the drug. Objective and methods Previous studies focused on changes in SERT binding, which might not necessarily reflect changes in SERT protein. Therefore, we compared levels of SERT protein, using a quantitative Western blot procedure, in autopsied brain (striatum, cerebral cortices) of chronic human cocaine users (n = 9), who all tested positive for the drug/metabolite in brain, to those in control subjects (n = 15) and, as a separate drug of abuse group, in chronic heroin users (n = 11). Results We found no significant difference in protein levels of SERT or the serotonin synthesizing enzyme tryptophan hydroxylase-2 among the control and drug abuse groups. In the cocaine users, no significant correlations were observed between SERT and brain levels of cocaine plus metabolites, or with levels of serotonin or its metabolite 5-hydroxyindoleacetic acid. Conclusion Our postmortem data suggest that a robust increase in striatal/cerebral cortical SERT protein is not a common characteristic of chronic, human cocaine users. Keywords Serotonin transporter . Cocaine . Heroin . Postmortem human brain . Western blot
Introduction Efforts to understand the mechanisms of action of the abused psychostimulant cocaine have mostly focused on the ability of the drug to influence activity of the brain dopamine
neurotransmitter system via its inhibition of the dopamine transporter (DAT) (see (Heal et al. 2014; Howell and Negus 2014)). However, over the decades, there has also been continuing interest in establishing whether some behaviors associated with cocaine use might be explained by its actions on
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00213-020-05562-4) contains supplementary material, which is available to authorized users. * Junchao Tong [email protected]
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Addiction Imaging Research Group, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada
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Division of Neuropathology, London Health Sciences Centre, University of Western Ontario, London, ON, Canada
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Section of Biopsychology, Department of Psychology, Centre for Addiction and Mental Health, Campbell Family
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