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

• Published in: Biological psychiatry (1969) Vol. 53; no. 7; pp. 585 - 592
• Main Authors: Dean, Brian, Bradbury, Robyn, Copolov, David Leon
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.04.2003; Elsevier Science
• Subjects: Adult; Adult and adolescent clinical studies; Analysis of Variance; Autopsy; Biological and medical sciences; Biomarkers - analysis; Cannabinoids - metabolism; Cannabis; Caudate Nucleus - metabolism; caudate-putamen; Central Nervous System - metabolism; Dopamine; Dopamine - metabolism; Dopamine Plasma Membrane Transport Proteins; Dronabinol - blood; Drug addictions; Female; Humans; hydroxylase; Male; Medical sciences; Membrane Glycoproteins; Membrane Transport Proteins - analysis; Middle Aged; Nerve Tissue Proteins; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Schizophrenia; Schizophrenia - blood; Schizophrenia - metabolism; substantia nigra; Toxicology; transporter; Tropical medicine; tyrosine; Tyrosine 3-Monooxygenase - analysis; Australia; Oceania; substantia nigra; Dopamine; caudate-putamen; transporter; cannabis; tyrosine; schizophrenia; hydroxylase; Human; Enzyme; Postmortem; Central nervous system; Biological marker; Schizophrenia; Exploration; Cannabidaceae; Cannabinoid; Tyrosine 3-monooxygenase; Putamen; Psychosis; Cannabis; Locus niger; Caudate nucleus; Dicotyledones; Angiospermae; Immunoblotting assay; Spermatophyta; Oxidoreductases; Presynaptic
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/S0006-3223(02)01545-7

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 Δ 9(−)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. 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. 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. 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.