Conditional knockout of NMDA receptors in dopamine neurons prevents nicotine-conditioned place preference.

Hdl Handle:
http://hdl.handle.net/10675.2/156
Title:
Conditional knockout of NMDA receptors in dopamine neurons prevents nicotine-conditioned place preference.
Authors:
Wang, Lei Phillip; Li, Fei; Shen, Xiaoming; Tsien, Joe Z.
Abstract:
Nicotine from smoking tobacco produces one of the most common forms of addictive behavior and has major societal and health consequences. It is known that nicotine triggers tobacco addiction by activating nicotine acetylcholine receptors (nAChRs) in the midbrain dopaminergic reward system, primarily via the ventral tegmental area. Heterogeneity of cell populations in the region has made it difficult for pharmacology-based analyses to precisely assess the functional significance of glutamatergic inputs to dopamine neurons in nicotine addiction. By generating dopamine neuron-specific NR1 knockout mice using cre/loxP-mediated method, we demonstrate that genetic inactivation of the NMDA receptors in ventral tegmental area dopamine neurons selectively prevents nicotine-conditioned place preference. Interestingly, the mutant mice exhibit normal performances in the conditioned place aversion induced by aversive air puffs. Therefore, this selective effect on addictive drug-induced reinforcement behavior suggests that NMDA receptors in the dopamine neurons are critical for the development of nicotine addiction.
Citation:
PLoS One. 2010 Jan 7; 5(1):e8616
Issue Date:
11-Jan-2010
URI:
http://hdl.handle.net/10675.2/156
DOI:
10.1371/journal.pone.0008616
PubMed ID:
20062537
PubMed Central ID:
PMC2797636
Type:
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
ISSN:
1932-6203
Appears in Collections:
Brain & Behavior Discovery Institute: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorWang, Lei Phillipen_US
dc.contributor.authorLi, Feien_US
dc.contributor.authorShen, Xiaomingen_US
dc.contributor.authorTsien, Joe Z.en_US
dc.date.accessioned2010-09-24T22:09:19Z-
dc.date.available2010-09-24T22:09:19Z-
dc.date.issued2010-01-11en_US
dc.identifier.citationPLoS One. 2010 Jan 7; 5(1):e8616en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid20062537en_US
dc.identifier.doi10.1371/journal.pone.0008616en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/156-
dc.description.abstractNicotine from smoking tobacco produces one of the most common forms of addictive behavior and has major societal and health consequences. It is known that nicotine triggers tobacco addiction by activating nicotine acetylcholine receptors (nAChRs) in the midbrain dopaminergic reward system, primarily via the ventral tegmental area. Heterogeneity of cell populations in the region has made it difficult for pharmacology-based analyses to precisely assess the functional significance of glutamatergic inputs to dopamine neurons in nicotine addiction. By generating dopamine neuron-specific NR1 knockout mice using cre/loxP-mediated method, we demonstrate that genetic inactivation of the NMDA receptors in ventral tegmental area dopamine neurons selectively prevents nicotine-conditioned place preference. Interestingly, the mutant mice exhibit normal performances in the conditioned place aversion induced by aversive air puffs. Therefore, this selective effect on addictive drug-induced reinforcement behavior suggests that NMDA receptors in the dopamine neurons are critical for the development of nicotine addiction.en_US
dc.rightsThe PMC Open Access Subset is a relatively small part of the total collection of articles in PMC. Articles in the PMC Open Access Subset are still protected by copyright, but are made available under a Creative Commons or similar license that generally allows more liberal redistribution and reuse than a traditional copyrighted work. Please refer to the license statement in each article for specific terms of use. The license terms are not identical for all articles in this subset.en_US
dc.subject.meshAnimalsen_US
dc.subject.meshConditioning, Operanten_US
dc.subject.meshDopamine / metabolismen_US
dc.subject.meshGene Knockout Techniquesen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Knockouten_US
dc.subject.meshNeurons / metabolismen_US
dc.subject.meshNicotine / administration & dosageen_US
dc.subject.meshReceptors, N-Methyl-D-Aspartate / genetics / physiologyen_US
dc.titleConditional knockout of NMDA receptors in dopamine neurons prevents nicotine-conditioned place preference.en_US
dc.typeJournal Articleen_US
dc.typeResearch Support, N.I.H., Extramuralen_US
dc.typeResearch Support, Non-U.S. Gov'ten_US
dc.identifier.pmcidPMC2797636en_US
dc.contributor.corporatenameBrain & Behavior Discovery Instituteen_US
dc.contributor.corporatenameDepartment of Neurologyen_US

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