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Brain dopamine transporter messenger RNA and binding sites in cocaine users: a postmortem study
K Y Little1, D P McLaughlin, L Zhang
1Department of Psychiatry, University of Michigan, and Ann Arbor Veterans Affairs Medical Center, 48105, USA. kylittle@umich.edu
Archives of General Psychiatry
|September 15, 1998
Summary
Chronic cocaine use increases dopamine transporter (DAT) binding sites in the striatum but paradoxically decreases DAT messenger RNA in the midbrain. These findings suggest complex mechanisms underlying cocaine
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Chronic cocaine exposure is suggested to increase dopamine transporter (DAT) synthesis in the human striatum.
- Radioligand binding studies show variable results for detecting cocaine binding site increases.
- This study investigates the relationship between midbrain DAT messenger RNA and striatal DAT binding sites in human cocaine users.
Purpose of the Study:
- To test the hypothesis that midbrain DAT messenger RNA synthesis increases in parallel with striatal DAT binding sites in cocaine users.
- To elucidate the complex mechanisms of cocaine's effect on DAT function.
Main Methods:
- Autopsy samples from human cocaine users (n=34) and controls (n=36) were analyzed.
- In situ hybridization quantified DAT messenger RNA in medial and lateral midbrain regions.
- Quantitative autoradiography assessed striatal DAT binding sites using [3H]WIN 35428.
Main Results:
- Cocaine users exhibited markedly increased striatal DAT binding sites.
- Medial midbrain DAT messenger RNA levels were paradoxically decreased in cocaine users.
Conclusions:
- Cocaine exposure significantly impacts DAT function.
- The underlying mechanisms of cocaine's effects on DAT are complex and warrant further investigation.