 |
|
Brain Dopamine Transporter Messenger RNA and Binding Sites in Cocaine Users
A Postmortem Study
Karley Y. Little, MD;
Daniel P. McLaughlin, PhD;
Lian Zhang, PhD;
Patrick R. McFinton, BS;
Gregory W. Dalack, MD;
Edwin H. Cook Jr, MD;
Bader J. Cassin, MD;
Stanley J. Watson, MD, PhD
Arch Gen Psychiatry. 1998;55:793-799.
Background Results of recent radioligand binding experiments suggest that chronic cocaine exposure increases dopamine transporter (DAT) synthesis throughout the striatum of humans. However, detection of cocaine binding site increases in animals and humans has varied depending on the radioligand used. The present experiment tested the hypothesis in cocaine-using humans that synthesis of midbrain DAT messenger RNA increases parallel with increased striatal DAT binding sites.
Methods Striatal and midbrain samples were collected during autopsy examination from human cocaine users (n=34) and from age-, sex-, and race-matched control subjects (n=36). Levels of DAT messenger RNA were quantified in the medial and lateral midbrain regions using in situ hybridization, and striatal DAT binding sites were assessed by quantitative autoradiography using the DAT-specific radioligand [3H]WIN 35428.
Results Striatal DAT binding sites were markedly increased in cocaine users, but, paradoxically, medial DAT messenger RNA levels were decreased.
Conclusion Cocaine exposure has a marked effect on DAT function, but the mechanisms involved may be complex.
From the Department of Psychiatry, University of Michigan (Drs Little, Zhang, Dalack, and Watson and Mr McFinton), Ann Arbor Veterans Affairs Medical Center (Drs Little and Dalack), and Mental Health Research Institute (Drs McLaughlin and Watson), Ann Arbor, Mich; the Department of Psychiatry, University of Chicago, Chicago, Ill (Dr Cook); and Office of Wayne County Medical Examiner, Detroit, Mich (Dr Cassin).
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Dysregulation of Dopamine Transporter Trafficking and Function after Abstinence from Cocaine Self-Administration in Rats: Evidence for Differential Regulation in Caudate Putamen and Nucleus Accumbens
Samuvel et al.
J. Pharmacol. Exp. Ther. 2008;325:293-301.
ABSTRACT
| FULL TEXT
Cocaine Abusers Have an Overexpression of alpha -Synuclein in Dopamine Neurons
Mash et al.
J. Neurosci. 2003;23:2564-2571.
ABSTRACT
| FULL TEXT
Catechol-O-Methyltransferase Genotype and Dopamine Regulation in the Human Brain
Akil et al.
J. Neurosci. 2003;23:2008-2013.
ABSTRACT
| FULL TEXT
Slowing Parkinson's disease progression: Recent dopamine agonist trials
Ahlskog
Neurology 2003;60:381-389.
ABSTRACT
| FULL TEXT
Loss of Striatal Vesicular Monoamine Transporter Protein (VMAT2) in Human Cocaine Users
Little et al.
Am. J. Psychiatry 2003;160:47-55.
ABSTRACT
| FULL TEXT
Decreased expression of the transcription factor NURR1 in dopamine neurons of cocaine abusers
Bannon et al.
Proc. Natl. Acad. Sci. USA 2002;99:6382-6385.
ABSTRACT
| FULL TEXT
Cocaine Induction of Dopamine Transporter Trafficking to the Plasma Membrane
Little et al.
Mol. Pharmacol. 2002;61:436-445.
ABSTRACT
| FULL TEXT
Progression of Changes in Dopamine Transporter Binding Site Density as a Result of Cocaine Self-Administration in Rhesus Monkeys
Letchworth et al.
J. Neurosci. 2001;21:2799-2807.
ABSTRACT
| FULL TEXT
Drug Interactions with the Dopamine Transporter in Cryopreserved Human Caudate
Eshleman et al.
J. Pharmacol. Exp. Ther. 2001;296:442-449.
ABSTRACT
| FULL TEXT
Addiction and the brain: the role of neurotransmitters in the cause and treatment of drug dependence
Tomkins and Sellers
CMAJ 2001;164:817-821.
ABSTRACT
| FULL TEXT
Elevated Central Serotonin Transporter Binding Availability in Acutely Abstinent Cocaine-Dependent Patients
Jacobsen et al.
Am. J. Psychiatry 2000;157:1134-1140.
ABSTRACT
| FULL TEXT
Striatal Dopaminergic Abnormalities in Human Cocaine Users
Little et al.
Am. J. Psychiatry 1999;156:238-245.
ABSTRACT
| FULL TEXT
Decreased expression of the transcription factor NURR1 in dopamine neurons of cocaine abusers
Bannon et al.
Proc. Natl. Acad. Sci. USA 2002;99:6382-6385.
ABSTRACT
| FULL TEXT
|
