Decreased brain dopamine cell numbers in human cocaine users

@article{Little2009DecreasedBD,
  title={Decreased brain dopamine cell numbers in human cocaine users},
  author={Karley Y. Little and Eric Ramssen and Ryan M. Welchko and Vitaly Volberg and Courtney J. Roland and B J Cassin},
  journal={Psychiatry Research},
  year={2009},
  volume={168},
  pages={173-180}
}
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TLDR
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Region-Specific Reductions in Morphometric Properties and Synaptic Colocalization of Astrocytes Following Cocaine Self-Administration and Extinction
TLDR
An assessment of the effects of cocaine self-administration on morphometric properties and synaptic colocalization of astrocyte peripheral processes in the prelimbic region of the medial prefrontal cortex and basolateral nucleus of the amygdala, both known to also contribute significantly to motivated behaviors are extended.
Cellular and molecular responses to acute cocaine treatment in neuronal-like N2a cells: potential mechanism for its resistance in cell death
TLDR
The data clearly indicate that Neuro-2a (N2a) cells employed a detoxifying strategy against cocaine, and extrapolating the knowledge of neuronal resistance to central nervous system (CNS) diseases could delay their onset or progression.
N-Acetyl Cysteine Mitigates the Acute Effects of Cocaine-Induced Toxicity in Astroglia-Like Cells
TLDR
All of the above identified features are significantly altered by cocaine, and may collectively represent the key pathology underlying acute toxicity-mediated death of astroglia-like cells and suggest that compounds which target and mitigate these early toxic changes in astrocytes could have a potentially broad therapeutic role in cocaine-induced CNS damage.
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References

SHOWING 1-10 OF 72 REFERENCES
Striatal dopaminergic abnormalities in human cocaine users.
TLDR
The present results confirm that cocaine users have a high number of dopamine transporter binding sites on dopaminergic neurons, despite an apparent low number of total dopamine terminals.
Loss of striatal vesicular monoamine transporter protein (VMAT2) in human cocaine users.
TLDR
Human cocaine users lose VMAT2 protein, which might reflect damage to striatal dopamine fibers, which could play a role in causing disordered mood and motivational processes in more severely dependent patients.
Dopamine transport function is elevated in cocaine users
TLDR
Evidence that DAT function is elevated by chronic cocaine abuse is presented and DA uptake function assayed in cryopreserved human brain synaptosomes is demonstrated to be a suitable approach for testing hypotheses of the mechanisms underlying human brain disorders and for studying the actions of addictive drugs in man.
Cocaine abuse elevates alpha-synuclein and dopamine transporter levels in the human striatum
TLDR
Concomitant regulation of &agr;-synuclein and dopamine transporter binding and function in human striatal synaptic terminals isolated from cocaine abusers is demonstrated.
Striatal dopamine, dopamine transporter, and vesicular monoamine transporter in chronic cocaine users
TLDR
The data suggest that chronic cocaine use is associated with modestly reduced levels of striatal DA and the DA transporter in some subjects and that these changes might contribute to the neurological and psychiatric effects of the drug.
Cocaine Uptake Is Decreased in the Brain of Detoxified Cocaine Abusers
Lack of neurochemical evidence for neurotoxic effects of repeated cocaine administration in rats on brain monoamine neurons.
Cocaine induction of dopamine transporter trafficking to the plasma membrane.
TLDR
The present model system may further the understanding of regulatory alterations in DAT radioligand binding and function caused by cocaine exposure and Immunofluorescence and biotinylation experiments indicated that cocaine treatment induced increases in plasma membrane DAT immunoreactivity and intracellular decreases.
Cocaine increases dopamine uptake and cell surface expression of dopamine transporters.
TLDR
Cocaine-induced increases in cell surface expression of DAT and associated changes in DA clearance represent a novel mechanism that may play a role in its addictive properties.
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