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Cannabis-sensitive dopaminergic markers in postmortem central nervous system: changes in schizophrenia
Brian Dean1, Robyn Bradbury, David Leon Copolov
1The Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute of Victoria, Parkville, Victoria, Australia.
Biological Psychiatry
|April 8, 2003
Summary
Schizophrenia patients with no detectable THC in their blood showed reduced dopamine transporter (DAT) in the caudate. Cannabis use may reverse this DAT reduction in schizophrenia.
Area of Science:
- Neuroscience
- Psychiatry
- Pharmacology
Background:
- Investigates pre-synaptic markers (dopamine transporter [DAT], tyrosine hydroxylase [TH]) in schizophrenia.
- Focuses on caudate nucleus changes in relation to Delta(9)-tetrahydrocannabinol (THC) presence.
- Animal studies suggest THC reduces dopamine uptake and TH in the striatum.
Purpose of the Study:
- To determine if pre-synaptic dopaminergic markers (DAT, TH) are altered in the caudate of schizophrenia subjects with and without THC exposure.
- To explore the potential modulatory effect of THC on DAT and TH levels in schizophrenia.
Main Methods:
- Postmortem caudate tissue from 14 schizophrenic and 14 control subjects.
- Autoradiography with [(3)H]mazindol to quantify dopamine transporter (DAT) binding.
- Western blotting with an anti-human TH antibody to measure tyrosine hydroxylase (TH) levels.
Main Results:
- Significantly decreased DAT binding in the caudate of THC-negative schizophrenic subjects compared to THC-negative controls (p =.01).
- No significant differences in DAT levels were observed between schizophrenic and control subjects with detectable THC in their blood.
- Tyrosine hydroxylase (TH) levels did not differ across any diagnostic or THC exposure groups.
Conclusions:
- Dopamine transporter (DAT) is reduced in the caudate of schizophrenia subjects not exposed to THC.
- Ingestion of THC from cannabis may potentially reverse the observed decrease in DAT in schizophrenia.