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Related Experiment Videos

Striatal dopaminergic abnormalities in human cocaine users

K Y Little1, L Zhang, T Desmond

  • 1Department of Psychiatry, University of Michigan, Ann Arbor VA Medical Center 48105, USA. kylittle@umich.edu

The American Journal of Psychiatry
|February 16, 1999
PubMed
Summary

Chronic cocaine use increases dopamine transporter sites in the striatum, despite a reduction in overall dopamine terminals. These changes may explain mood and behavioral issues in users.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Addiction Research

Background:

  • Previous studies indicated elevated dopamine uptake sites in chronic cocaine users' striatum, potentially linked to withdrawal symptoms like depression.
  • Inconsistencies in prior research may stem from radioligand affinity variations or concurrent dopamine neuron loss.

Purpose of the Study:

  • To investigate differences in dopamine transporter (DAT) binding sites and affinity in postmortem striatal samples from cocaine users and controls.
  • To assess total dopaminergic terminals using vesicular monoamine transporter (VMAT2) binding.

Main Methods:

  • Assayed cocaine analog [3H]WIN 35428 binding to DAT in striatal samples from 15 cocaine users and 15 matched controls.
  • Measured VMAT2 binding using (+)-[3H]dihydrotetrabenazine (DTBZ) as an indicator of dopaminergic terminals.

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Main Results:

  • Cocaine users exhibited significantly higher striatal [3H]WIN 35428 binding (Bmax = 9.0 fmol/µg protein) compared to controls (Bmax = 6.0 fmol/µg protein).
  • Severity of cocaine use correlated positively with [3H]WIN 35428 binding levels.
  • Cocaine users showed significantly lower [3H]DTBZ binding (330 nCi/mg) than controls (374 nCi/mg).

Conclusions:

  • Confirms elevated dopamine transporter binding sites in chronic cocaine users.
  • Reveals a decrease in total dopaminergic terminals, indicated by lower VMAT2 binding.
  • Suggests these neuroadaptations contribute to the characteristic subjective and behavioral abnormalities in chronic cocaine abuse.