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Original article| Volume 53, ISSUE 7, P585-592, April 01, 2003

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Cannabis-sensitive dopaminergic markers in postmortem central nervous system: changes in schizophrenia

  • Brian Dean
    Correspondence
    Address reprint requests to Brian Dean, The Rebecca L. Cooper Research Laboratories, Mental Health Research Institute of Victoria, Locked Bag 11, Parkville, Victoria3052Australia.
    Affiliations
    The Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute of Victoria, Parkville, Victoria, Australia
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  • Robyn Bradbury
    Affiliations
    The Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute of Victoria, Parkville, Victoria, Australia
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  • David Leon Copolov
    Affiliations
    The Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute of Victoria, Parkville, Victoria, Australia
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      Abstract

      Background

      This study investigated if changes in pre-synaptic markers on dopaminergic neurons (dopamine transporter [DAT], tyrosine hydroxylase [TH]) were present in the caudate from subjects with schizophrenia who had Δ9(−)tetrahydrocannabinol (THC) in their blood at autopsy. These changes were posited because animal studies show that treatment with THC decreases dopamine uptake and TH in the striatum.

      Methods

      Studies utilized caudate, obtained postmortem, from 14 schizophrenic and 14 control subjects. [3H]mazindol binding to caudate, measured using autoradiography, was taken as a measure of DAT; TH levels were estimated using an antihuman TH antibody and Western blotting.

      Results

      There was decreased [3H]mazindol binding to DAT in the caudate from the schizophrenic subjects with no detectable blood THC levels (THC(−)) compared with THC(−) control subjects (mean ± SEM: 240 ± 19 vs. 296 ± 14 fmol/mg estimated tissue equivalents, p = .01). There were no significant differences between levels of DAT in the caudate from schizophrenic and control subjects that had THC in their blood. Tyrosine hyroxylase was not different in any diagnostic cohort.

      Conclusions

      Our data suggests that DAT is decreased in the caudate from THC(−) subjects with schizophrenia, a change that may be reversed by ingesting THC from cannabis.

      Keywords

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