Document Detail


A corticotropin releasing factor pathway for ethanol regulation of the ventral tegmental area in the bed nucleus of the stria terminalis.
MedLine Citation:
PMID:  23325234     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A growing literature suggests that catecholamines and corticotropin-releasing factor (CRF) interact in a serial manner to activate the bed nucleus of the stria terminalis (BNST) to drive stress- or cue-induced drug- and alcohol-seeking behaviors. Data suggest that these behaviors are driven in part by BNST projections to the ventral tegmental area (VTA). Together, these findings suggest the existence of a CRF-signaling pathway within the BNST that is engaged by catecholamines and regulates the activity of BNST neurons projecting to the VTA. Here we test three aspects of this model to determine: (1) whether catecholamines modify CRF neuron activity in the BNST; (2) whether CRF regulates excitatory drive onto VTA-projecting BNST neurons; and (3) whether this system is altered by ethanol exposure and withdrawal. A CRF neuron fluorescent reporter strategy was used to identify BNST CRF neurons for whole-cell patch-clamp analysis in acutely prepared slices. Using this approach, we found that both dopamine and isoproterenol significantly depolarized BNST CRF neurons. Furthermore, using a fluorescent microsphere-based identification strategy we found that CRF enhances the frequency of spontaneous EPSCs onto VTA-projecting BNST neurons in naive mice. This action of CRF was occluded during acute withdrawal from chronic intermittent ethanol exposure. These findings suggest that dopamine and isoproterenol may enhance CRF release from local BNST sources, leading to enhancement of excitatory neurotransmission on VTA-projecting neurons, and that this pathway is engaged by patterns of alcohol exposure and withdrawal known to drive excessive alcohol intake.
Authors:
Yuval Silberman; Robert T Matthews; Danny G Winder
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  33     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-17     Completed Date:  2013-04-01     Revised Date:  2013-07-18    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  950-60     Citation Subset:  IM    
Affiliation:
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-Agonists / pharmacology
Animals
Corticotropin-Releasing Hormone / metabolism*
Dopamine / pharmacology
Ethanol / pharmacology*
Female
Isoproterenol / pharmacology
Male
Mice
Mice, Transgenic
Neural Pathways / metabolism
Neurons / drug effects*,  metabolism
Septal Nuclei / drug effects*,  metabolism
Ventral Tegmental Area / drug effects*,  metabolism
Grant Support
ID/Acronym/Agency:
AA19455/AA/NIAAA NIH HHS; AA20140/AA/NIAAA NIH HHS; DA19112/DA/NIDA NIH HHS; R01 AA019455/AA/NIAAA NIH HHS; R01 DA019112/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Adrenergic beta-Agonists; 64-17-5/Ethanol; 7683-59-2/Isoproterenol; 9015-71-8/Corticotropin-Releasing Hormone
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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