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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
35
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pubmed:dateCreated |
2011-9-1
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pubmed:abstractText |
The mesostriatal dopamine (DA) system contributes to several aspects of responses to rewarding substances and is implicated in conditions such as drug addiction and eating disorders. A subset of DA neurons has been shown to express the type 2 Vesicular glutamate transporter (Vglut2) and may therefore corelease glutamate. In the present study, we analyzed mice with a conditional deletion of Vglut2 in DA neurons (Vglut2(f/f;DAT-Cre)) to address the functional significance of the glutamate-DA cophenotype for responses to cocaine and food reinforcement. Biochemical parameters of striatal DA function were also examined by using DA receptor autoradiography, immediate-early gene quantitative in situ hybridization after cocaine challenge, and DA-selective in vivo chronoamperometry. Mice in which Vglut2 expression had been abrogated in DA neurons displayed enhanced operant self-administration of both high-sucrose food and intravenous cocaine. Furthermore, cocaine seeking maintained by drug-paired cues was increased by 76%, showing that reward-dependent plasticity is perturbed in these mice. In addition, several lines of evidence suggest that adaptive changes occurred in both the ventral and dorsal striatum in the absence of VGLUT2: DA receptor binding was increased, and basal mRNA levels of the DA-induced early genes Nur77 and c-fos were elevated as after cocaine induction. Furthermore, in vivo challenge of the DA system by potassium-evoked depolarization revealed less DA release in both striatal areas. This study demonstrates that absence of VGLUT2 in DA neurons leads to perturbations of reward consumption as well as reward-associated memory, features of particular relevance for addictive-like behavior.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cocaine,
http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Plasma Membrane Transport...,
http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Uptake Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Nr4a1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Subfamily 4...,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Chloride,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-fos,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Dopamine,
http://linkedlifedata.com/resource/pubmed/chemical/Slc17a6 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Sucrose,
http://linkedlifedata.com/resource/pubmed/chemical/Vesicular Glutamate Transport...
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1529-2401
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pubmed:author |
pubmed-author:AlsiöJohanJ,
pubmed-author:ArvidssonEmmaE,
pubmed-author:BirgnerCarolinaC,
pubmed-author:DescarriesLaurentL,
pubmed-author:FortinGuillaume MGM,
pubmed-author:HalboutBriacB,
pubmed-author:KullanderKlasK,
pubmed-author:LévesqueDanielD,
pubmed-author:MahmoudiSouhaS,
pubmed-author:NordenankarKarinK,
pubmed-author:OlsonLarsL,
pubmed-author:SmithCaseyC,
pubmed-author:TrudeauLouis-ÉricLÉ,
pubmed-author:Wallén-MackenzieAsaA
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pubmed:issnType |
Electronic
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pubmed:day |
31
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pubmed:volume |
31
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
12593-603
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pubmed:meshHeading |
pubmed-meshheading:21880920-Analysis of Variance,
pubmed-meshheading:21880920-Animals,
pubmed-meshheading:21880920-Autoradiography,
pubmed-meshheading:21880920-Behavior, Addictive,
pubmed-meshheading:21880920-Behavior, Animal,
pubmed-meshheading:21880920-Cell Death,
pubmed-meshheading:21880920-Cocaine,
pubmed-meshheading:21880920-Conditioning, Operant,
pubmed-meshheading:21880920-Cues,
pubmed-meshheading:21880920-Dopamine,
pubmed-meshheading:21880920-Dopamine Plasma Membrane Transport Proteins,
pubmed-meshheading:21880920-Dopamine Uptake Inhibitors,
pubmed-meshheading:21880920-Electrochemical Techniques,
pubmed-meshheading:21880920-Food Preferences,
pubmed-meshheading:21880920-Gene Expression Regulation,
pubmed-meshheading:21880920-Male,
pubmed-meshheading:21880920-Mesencephalon,
pubmed-meshheading:21880920-Mice,
pubmed-meshheading:21880920-Mice, Inbred C57BL,
pubmed-meshheading:21880920-Mice, Transgenic,
pubmed-meshheading:21880920-Neurons,
pubmed-meshheading:21880920-Nuclear Receptor Subfamily 4, Group A, Member 1,
pubmed-meshheading:21880920-Potassium Chloride,
pubmed-meshheading:21880920-Protein Binding,
pubmed-meshheading:21880920-Proto-Oncogene Proteins c-fos,
pubmed-meshheading:21880920-RNA, Messenger,
pubmed-meshheading:21880920-Receptors, Dopamine,
pubmed-meshheading:21880920-Reinforcement Schedule,
pubmed-meshheading:21880920-Reward,
pubmed-meshheading:21880920-Self Administration,
pubmed-meshheading:21880920-Sucrose,
pubmed-meshheading:21880920-Vesicular Glutamate Transport Protein 2
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pubmed:year |
2011
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pubmed:articleTitle |
Enhanced sucrose and cocaine self-administration and cue-induced drug seeking after loss of VGLUT2 in midbrain dopamine neurons in mice.
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pubmed:affiliation |
Department of Neuroscience, Unit of Developmental Genetics, Uppsala University, S-751 24 Uppsala, Sweden.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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