Document Detail


Decreased Vesicular Monoamine Transporter Type 2 Availability in the Striatum Following Chronic Cocaine Self-Administration in Nonhuman Primates.
MedLine Citation:
PMID:  25062684     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: Consistent with postmortem data, in a recent positron emission tomography study, we demonstrated less [(11)C]-(+)-dihydrotetrabenazine ([(11)C]DTBZ) binding to striatal vesicular monoamine transporter type 2 (VMAT2) in cocaine abusers compared with control subjects. A major limitation of these between-group comparison human studies is their inability to establish a causal relationship between cocaine abuse and lower VMAT2. Furthermore, studies in rodents that evaluated VMAT2 binding before and after cocaine self-administration do not support a reduction in VMAT2.
METHODS: To clarify these discrepant VMAT2 findings and attribute VMAT2 reduction to cocaine abuse, we imaged four rhesus monkeys with [(11)C]DTBZ positron emission tomography before and after 16 months of cocaine self-administration. [(11)C]DTBZ binding potential in the striatum was derived using the simplified reference tissue method with the occipital cortex time activity curve as an input function.
RESULTS: Chronic cocaine self-administration led to a significant (25.8 ± 7.8%) reduction in [(11)C]DTBZ binding potential.
CONCLUSIONS: In contrast to the cocaine rodent investigations that do not support alterations in VMAT2, these results in nonhuman primates clearly demonstrated a reduction in VMAT2 binding following prolonged exposure to cocaine. Lower VMAT2 implies that fewer dopamine storage vesicles are available in the presynaptic terminals for release, a likely factor contributing to decreased dopamine transmission in cocaine dependence. Future studies should attempt to clarify the clinical significance of lower VMAT2 in cocaine abusers, for example, its relationship to relapse and vulnerability to mood disorders.
Authors:
Rajesh Narendran; Hank P Jedema; Brian J Lopresti; Neale Scott Mason; Michael L Himes; Charles W Bradberry
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-6-23
Journal Detail:
Title:  Biological psychiatry     Volume:  -     ISSN:  1873-2402     ISO Abbreviation:  Biol. Psychiatry     Publication Date:  2014 Jun 
Date Detail:
Created Date:  2014-7-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0213264     Medline TA:  Biol Psychiatry     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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