Journal Article

Increased vulnerability to cocaine in mice lacking dopamine D 3 receptors

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

2012

Overview

Neuroimaging studies using positron emission tomography suggest that reduced dopamine D 2 receptor availability in the neostriatum is associated with increased vulnerability to drug addiction in humans and experimental animals. The role of D 3 receptors (D 3 Rs) in the neurobiology of addiction remains unclear, however. Here we report that D 3 R KO (D 3 −/− ) 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 D 3 −/− mice. In addition, D 3 −/− 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 D 3 R deletion increases vulnerability to cocaine, and that reduced D 3 R availability in the brain may constitute a risk factor for the development of cocaine addiction.