Document Detail


Rostroventral caudate putamen involvement in ethanol withdrawal is influenced by a chromosome 4 locus.
MedLine Citation:
PMID:  20608999     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Physiological dependence and associated withdrawal episodes are thought to constitute a motivational force that sustains alcohol use and abuse and may contribute to relapse in dependent individuals. Although no animal model duplicates alcoholism, models for specific factors, like withdrawal, are useful for identifying potential genetic and neural determinants of liability in humans. Previously, we identified a quantitative trait locus (QTL) and gene (Mpdz, which encodes the multi-PDZ domain protein) on chromosome 4 with a large effect on alcohol withdrawal in mice. Using congenic mice that confirm this QTL and c-Fos expression as a high-resolution marker of neuronal activation, we report that congenic mice show significantly less neuronal activity associated with alcohol withdrawal in the rostroventral caudate putamen (rvCP), but not other parts of the striatum, compared with background strain mice. Moreover, bilateral rvCP lesions significantly increase alcohol withdrawal severity. Using retrograde (fluorogold) and anterograde (Texas Red conjugated dextran amine) tract tracing, we found that ∼25% of c-Fos immunoreactive rvCP neurons project to caudolateral substantia nigra pars reticulata (clSNr), which we previously found is crucially involved in withdrawal following acute and repeated alcohol exposure. Our results expand upon work suggesting that this QTL impacts alcohol withdrawal via basal ganglia circuitry associated with limbic function, and indicate that an rvCP-clSNr projection plays a critical role. Given the growing body of evidence that the syntenic region of human chromosome 9p and human MPDZ gene are associated with alcohol abuse, our results may facilitate research on alcohol dependence and associated withdrawal in clinical populations.
Authors:
G Chen; K J Buck
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-09-01
Journal Detail:
Title:  Genes, brain, and behavior     Volume:  9     ISSN:  1601-183X     ISO Abbreviation:  Genes Brain Behav.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-11-02     Completed Date:  2011-02-08     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  101129617     Medline TA:  Genes Brain Behav     Country:  England    
Other Details:
Languages:  eng     Pagination:  768-76     Citation Subset:  IM    
Copyright Information:
© 2010 The Authors. Genes, Brain and Behavior © 2010 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.
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MeSH Terms
Descriptor/Qualifier:
Animals
Behavior, Animal / physiology
Carrier Proteins / genetics
Caudate Nucleus / physiology*
Central Nervous System Depressants / adverse effects*
Chromosomes, Mammalian / genetics*
Ethanol / adverse effects*
Immunohistochemistry
Mice
Mice, Congenic
Mice, Inbred DBA
Nerve Net / physiology
Proto-Oncogene Proteins c-fos / biosynthesis,  genetics
Putamen / physiology*
Quantitative Trait Loci
Stereotaxic Techniques
Substance Withdrawal Syndrome / genetics*,  physiopathology,  psychology
Grant Support
ID/Acronym/Agency:
AA011114/AA/NIAAA NIH HHS; AA10760/AA/NIAAA NIH HHS; P50 AA010760/AA/NIAAA NIH HHS; P50 AA010760-109005/AA/NIAAA NIH HHS; R01 AA011114/AA/NIAAA NIH HHS; R01 AA011114-12/AA/NIAAA NIH HHS; R01 DA005228/DA/NIDA NIH HHS; R01 DA005228-19/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Central Nervous System Depressants; 0/Mpdz protein, mouse; 0/Proto-Oncogene Proteins c-fos; 3K9958V90M/Ethanol
Comments/Corrections

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