Document Detail


Mesolimbic dopamine in desire and dread: enabling motivation to be generated by localized glutamate disruptions in nucleus accumbens.
MedLine Citation:
PMID:  18614688     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
An important issue in affective neuroscience concerns the role of mesocorticolimbic dopamine systems in positive-valenced motivation (e.g., reward) versus negative-valenced motivation (e.g., fear). Here, we assessed whether endogenous dopamine receptor stimulation in nucleus accumbens contributes to both appetitive behavior and fearful behavior that is generated in keyboard manner by local glutamate disruptions at different sites in medial shell. 6,7-Dinitroquinoxaline-2,3(1H,4H)-dione (DNQX) microinjections (450 ng) locally disrupt glutamate signals in <4 mm(3) of nucleus accumbens, and generate either desire or fear (or both) depending on precise rostrocaudal location in medial shell. At rostral shell sites, local AMPA/kainate blockade generates positive ingestive behavior, but the elicited motivated behavior becomes incrementally more fearful as the same microinjection is moved caudally. A dopamine-blocking mixture of D(1) and D(2) antagonists (raclopride and SCH-23390 [R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5,-tetrahydro-1H-3-benzazepine hydrochloride]) was combined here in the same microinjection with DNQX to assess the role of endogenous local dopamine in mediating the DNQX-motivated behaviors. We report that local dopamine blockade prevented DNQX microinjections from generating appetitive behavior (eating) in rostral shell, and equally prevented DNQX from generating fearful behavior (defensive treading) in caudal shell. We conclude that local dopamine is needed to enable disruptions of corticolimbic glutamate signals in shell to generate either positive incentive salience or negative fearful salience (valence depending on site and other conditions). Thus, dopamine interacts with localization of valence-biased glutamate circuits in medial shell to facilitate keyboard stimulation of both appetitive and fearful motivations.
Authors:
Alexis Faure; Sheila M Reynolds; Jocelyn M Richard; Kent C Berridge
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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:  28     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-07-10     Completed Date:  2008-08-12     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7184-92     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Behavior, Animal / drug effects
Dopamine / metabolism*
Dopamine Agents / pharmacology
Drug Interactions
Excitatory Amino Acid Agents / pharmacology
Fear / physiology*
Feeding Behavior / drug effects
Gene Expression / drug effects
Glutamic Acid / metabolism*
Limbic System / drug effects,  metabolism*
Male
Microinjections / methods
Motivation*
Nucleus Accumbens / drug effects,  metabolism*
Oncogene Proteins v-fos / metabolism
Rats
Rats, Sprague-Dawley
Grant Support
ID/Acronym/Agency:
DA15188/DA/NIDA NIH HHS; MH63649/MH/NIMH NIH HHS; R01 DA015188/DA/NIDA NIH HHS; R01 DA015188-05/DA/NIDA NIH HHS; R01 MH063649/MH/NIMH NIH HHS; R01 MH063649-01A2/MH/NIMH NIH HHS; R01 MH063649-05/MH/NIMH NIH HHS; R01 MH063649-06A1/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Dopamine Agents; 0/Excitatory Amino Acid Agents; 0/Oncogene Proteins v-fos; 3KX376GY7L/Glutamic Acid; VTD58H1Z2X/Dopamine
Comments/Corrections

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