Autor: |
Rui Song, Hai-Ying Zhang, Xia Li, Guo-Hua Bi, Gardner, Eliot L., Zheng-Xiong Xi |
Předmět: |
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Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; 10/23/2012, Vol. 109 Issue 43, p17675-17680, 6p |
Abstrakt: |
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 brain may constitute a risk factor for the development of cocaine addiction. [ABSTRACT FROM AUTHOR] |
Databáze: |
Complementary Index |
Externí odkaz: |
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