Increased vulnerability to cocaine in mice lacking dopamine D3 receptors

Rui Song, Haiying Zhang, Xia Li, Guo Hua Bi, Eliot L. Gardner, Zheng Xiong Xi

Research output: Contribution to journalArticle

Abstract

Neuroimaging studies using positron emission tomography suggest that reduced dopamine D2 receptor availability in the neostriatum is associated with increased vulnerability to drug addiction in humans and experimental animals. The role of D3 receptors (D3Rs) in the neurobiology of addiction remains unclear, however. Here we report that D3R KO (D3-/-) mice display enhanced cocaine self-administration and enhanced motivation for cocaine-taking and cocaine-seeking behavior. This increased vulnerability to cocaine is accompanied by decreased dopamine response to cocaine secondary to increased basal levels of extracellular dopamine in the nucleus accumbens, suggesting a compensatory response to decreased cocaine reward in D3-/- mice. In addition, D3-/- mice also display up-regulation of dopamine transporters in the striatum, suggesting a neuroadaptative attempt to normalize elevated basal extracellular dopamine. These findings suggest that D3R deletion increases vulnerability to cocaine, and that reduced D3R availability in the brainmay constitute a risk factor for the development of cocaine addiction.

Original languageEnglish (US)
Pages (from-to)17675-17680
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number43
DOIs
StatePublished - Oct 23 2012
Externally publishedYes

Fingerprint

Dopamine D3 Receptors
Cocaine
Dopamine
Neostriatum
Cocaine-Related Disorders
Dopamine Plasma Membrane Transport Proteins
Self Administration
Dopamine D2 Receptors
Neurobiology
Nucleus Accumbens
Reward
Neuroimaging
Positron-Emission Tomography
Substance-Related Disorders
Motivation
Up-Regulation

Keywords

  • Etiology of addiction
  • Extinction
  • Reinforcement
  • Reinstatement
  • Susceptibility to cocaine

ASJC Scopus subject areas

  • General

Cite this

Increased vulnerability to cocaine in mice lacking dopamine D3 receptors. / Song, Rui; Zhang, Haiying; Li, Xia; Bi, Guo Hua; Gardner, Eliot L.; Xi, Zheng Xiong.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 43, 23.10.2012, p. 17675-17680.

Research output: Contribution to journalArticle

Song, Rui ; Zhang, Haiying ; Li, Xia ; Bi, Guo Hua ; Gardner, Eliot L. ; Xi, Zheng Xiong. / Increased vulnerability to cocaine in mice lacking dopamine D3 receptors. In: Proceedings of the National Academy of Sciences of the United States of America. 2012 ; Vol. 109, No. 43. pp. 17675-17680.
@article{8c341c385bf5423f9b51673d618fa707,
title = "Increased vulnerability to cocaine in mice lacking dopamine D3 receptors",
abstract = "Neuroimaging studies using positron emission tomography suggest that reduced dopamine D2 receptor availability in the neostriatum is associated with increased vulnerability to drug addiction in humans and experimental animals. The role of D3 receptors (D3Rs) in the neurobiology of addiction remains unclear, however. Here we report that D3R KO (D3-/-) mice display enhanced cocaine self-administration and enhanced motivation for cocaine-taking and cocaine-seeking behavior. This increased vulnerability to cocaine is accompanied by decreased dopamine response to cocaine secondary to increased basal levels of extracellular dopamine in the nucleus accumbens, suggesting a compensatory response to decreased cocaine reward in D3-/- mice. In addition, D3-/- mice also display up-regulation of dopamine transporters in the striatum, suggesting a neuroadaptative attempt to normalize elevated basal extracellular dopamine. These findings suggest that D3R deletion increases vulnerability to cocaine, and that reduced D3R availability in the brainmay constitute a risk factor for the development of cocaine addiction.",
keywords = "Etiology of addiction, Extinction, Reinforcement, Reinstatement, Susceptibility to cocaine",
author = "Rui Song and Haiying Zhang and Xia Li and Bi, {Guo Hua} and Gardner, {Eliot L.} and Xi, {Zheng Xiong}",
year = "2012",
month = "10",
day = "23",
doi = "10.1073/pnas.1205297109",
language = "English (US)",
volume = "109",
pages = "17675--17680",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "43",

}

TY - JOUR

T1 - Increased vulnerability to cocaine in mice lacking dopamine D3 receptors

AU - Song, Rui

AU - Zhang, Haiying

AU - Li, Xia

AU - Bi, Guo Hua

AU - Gardner, Eliot L.

AU - Xi, Zheng Xiong

PY - 2012/10/23

Y1 - 2012/10/23

N2 - Neuroimaging studies using positron emission tomography suggest that reduced dopamine D2 receptor availability in the neostriatum is associated with increased vulnerability to drug addiction in humans and experimental animals. The role of D3 receptors (D3Rs) in the neurobiology of addiction remains unclear, however. Here we report that D3R KO (D3-/-) mice display enhanced cocaine self-administration and enhanced motivation for cocaine-taking and cocaine-seeking behavior. This increased vulnerability to cocaine is accompanied by decreased dopamine response to cocaine secondary to increased basal levels of extracellular dopamine in the nucleus accumbens, suggesting a compensatory response to decreased cocaine reward in D3-/- mice. In addition, D3-/- mice also display up-regulation of dopamine transporters in the striatum, suggesting a neuroadaptative attempt to normalize elevated basal extracellular dopamine. These findings suggest that D3R deletion increases vulnerability to cocaine, and that reduced D3R availability in the brainmay constitute a risk factor for the development of cocaine addiction.

AB - Neuroimaging studies using positron emission tomography suggest that reduced dopamine D2 receptor availability in the neostriatum is associated with increased vulnerability to drug addiction in humans and experimental animals. The role of D3 receptors (D3Rs) in the neurobiology of addiction remains unclear, however. Here we report that D3R KO (D3-/-) mice display enhanced cocaine self-administration and enhanced motivation for cocaine-taking and cocaine-seeking behavior. This increased vulnerability to cocaine is accompanied by decreased dopamine response to cocaine secondary to increased basal levels of extracellular dopamine in the nucleus accumbens, suggesting a compensatory response to decreased cocaine reward in D3-/- mice. In addition, D3-/- mice also display up-regulation of dopamine transporters in the striatum, suggesting a neuroadaptative attempt to normalize elevated basal extracellular dopamine. These findings suggest that D3R deletion increases vulnerability to cocaine, and that reduced D3R availability in the brainmay constitute a risk factor for the development of cocaine addiction.

KW - Etiology of addiction

KW - Extinction

KW - Reinforcement

KW - Reinstatement

KW - Susceptibility to cocaine

UR - http://www.scopus.com/inward/record.url?scp=84867902934&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84867902934&partnerID=8YFLogxK

U2 - 10.1073/pnas.1205297109

DO - 10.1073/pnas.1205297109

M3 - Article

C2 - 23045656

AN - SCOPUS:84867902934

VL - 109

SP - 17675

EP - 17680

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 43

ER -