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


METHODS
Studies utilized caudate, obtained postmortem, from 14 schizophrenic and 14 control subjects. [(3)H]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 [(3)H]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 hydroxylase 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.
Dean
Brian
B
The Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute of Victoria, Parkville, Victoria, Australia.
Bradbury
Robyn
R
Copolov
David Leon
DL
D000328:Adult; D000704:Analysis of Variance; D001344:Autopsy; D015415:Biomarkers / Q000032:analysis; D002186:Cannabinoids / Q000378:metabolism*; D002188:Cannabis; D002421:Caudate Nucleus / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D013759:Dronabinol / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000032:analysis; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D012559:Schizophrenia / Q000097:blood / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D015415:Biomarkers; D002186:Cannabinoids; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493214:SLC6A3 protein, human; D013759:Dronabinol; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine