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Serotonin transporters upregulate with chronic cocaine use
D C Mash1, J K Staley, S Izenwasser
1Department of Neurology, School of Medicine, University of Miami, Miami, FL 33136, USA. dmash@newssun.med.miami.edu
Journal of Chemical Neuroanatomy
|February 24, 2001
Summary
Chronic cocaine use alters serotonin transporter (SERT) levels in the brain. Cocaine overdose victims showed increased SERT, but those with excited delirium had distinct changes, suggesting unique phenotypes.
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- Cocaine inhibits serotonin reuptake, potentially causing serotonin-deficit dysregulation with chronic use.
- Serotonin modulates dopaminergic neurotransmission, impacting mood and behavior.
Purpose of the Study:
- To investigate the impact of chronic cocaine use on serotonin transporter (SERT) densities in specific brain regions.
- To differentiate SERT changes in cocaine overdose (CO) victims with and without excited delirium (ED).
Main Methods:
- Quantitative autoradiography using [125I]RTI-55 to measure SERT densities.
- Analysis of brain tissue from cocaine overdose victims and drug-free controls.
- Comparison of SERT levels in striatum, substantia nigra, amygdala, and paralimbic cortex.
Main Results:
- SERT densities were elevated in the nucleus accumbens and striatum of CO victims.
- ED victims showed increased SERT in anterior striatum but not posterior striatum.
- SERT was elevated in orbitofrontal gyrus, insular cortex, and cingulate gyrus in both CO and ED groups.
- Chronic cocaine exposure upregulated SERT in the substantia nigra of CO victims, but not ED victims.
Conclusions:
- Chronic cocaine use leads to adaptive upregulation of SERT in specific brain areas.
- Excited delirium may represent a distinct phenotype with altered SERT regulation.
- SERT changes may contribute to mood disturbances and craving during cocaine abstinence.