Junchao Tong1,2, Jeffrey H Meyer3, Isabelle Boileau4, Lee-Cyn Ang5, Paul J Fletcher6, Yoshiaki Furukawa7, Stephen J Kish8,3. 1. Preclinical Imaging, Brain Health Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada. Junchao.tong@camh.ca. 2. Human Brain Laboratory, Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada. Junchao.tong@camh.ca. 3. Brain Health Imaging Centre and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada. 4. Addiction Imaging Research Group, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada. 5. Division of Neuropathology, London Health Sciences Centre, University of Western Ontario, London, ON, Canada. 6. Section of Biopsychology, Department of Psychology, Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute, University of Toronto, Toronto, ON, Canada. 7. Department of Neurology, Juntendo Tokyo Koto Geriatric Medical Center, and Faculty of Medicine, University & Post Graduate University of Juntendo, Tokyo, Japan. 8. Human Brain Laboratory, Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
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.
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 humancocaine 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, humancocaine users.
Entities:
Keywords:
Cocaine; Heroin; Postmortem human brain; Serotonin transporter; Western blot
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