Brain dopamine transporter messenger RNA and binding sites in cocaine users: a postmortem study

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.