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

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 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.

• Authors: Brian Dean, Robyn Bradbury, David Leon Copolov
• Journal: Biological psychiatry (Biol Psychiatry) Vol. 53 Issue 7 Pg. 585-92 (Apr 01 2003) ISSN: 0006-3223 [Print] United States
• PMID: 12679236 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Cannabinoids
• Dopamine Plasma Membrane Transport Proteins
• Membrane Glycoproteins
• Membrane Transport Proteins
• Nerve Tissue Proteins
• SLC6A3 protein, human
• Dronabinol
• Tyrosine 3-Monooxygenase
• Dopamine

Topics

• Adult
• Analysis of Variance
• Autopsy
• Biomarkers (analysis)
• Cannabinoids (metabolism)
• Cannabis
• Caudate Nucleus (metabolism)
• Central Nervous System (metabolism)
• Dopamine (metabolism)
• Dopamine Plasma Membrane Transport Proteins
• Dronabinol (blood)
• Female
• Humans
• Male
• Membrane Glycoproteins
• Membrane Transport Proteins (analysis)
• Middle Aged
• Nerve Tissue Proteins
• Schizophrenia (blood, metabolism)
• Tyrosine 3-Monooxygenase (analysis)