Imaging Glutamate Homeostasis in Cocaine Addiction with the Metabotropic Glutamate Receptor 5 Positron Emission Tomography Radiotracer [11C]ABP688 and Magnetic Resonance Spectroscopy

被引:58
作者
Martinez, Diana [1 ,2 ]
Slifstein, Mark [1 ,2 ]
Nabulsi, Nabeel [3 ]
Grassetti, Alexander [1 ,2 ]
Urban, Nina B. L. [1 ,2 ]
Perez, Audrey [1 ,2 ]
Liu, Fei [1 ,2 ]
Lin, Shu-Fei [3 ]
Ropchan, Jim [3 ]
Mao, Xiangling [4 ]
Kegeles, Lawrence S. [1 ,2 ]
Shungu, Dikoma C. [4 ]
Carson, Richard E. [3 ]
Huang, Yiyun [3 ]
机构
[1] Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York, NY 10032 USA
[2] New York State Psychiat Inst & Hosp, New York, NY 10032 USA
[3] Yale Univ, Sch Med, Dept Psychiat, Yale Positron Emiss Tomog Ctr, New Haven, CT USA
[4] Cornell Univ, Dept Radiol, Weill Med Coll, New York, NY 10021 USA
关键词
Addiction; cocaine; cocaine self-administration; magnetic resonance spectroscopy; metabotropic glutamate receptor 5; positron emission tomography; INDUCED DOPAMINE RELEASE; GAMMA-AMINOBUTYRIC-ACID; MGLUR5 ANTAGONIST MPEP; IN-VIVO; FUNCTIONAL SUBDIVISIONS; INDUCED REINSTATEMENT; DEPENDENT PATIENTS; NUCLEUS-ACCUMBENS; SQUIRREL-MONKEYS; BINDING;
D O I
10.1016/j.biopsych.2013.06.026
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Background: Preclinical studies demonstrate that glutamate homeostasis in the striatum is disrupted following cocaine exposure, including a decrease in metabotropic glutamate receptor type 5 (mGluR5) expression and reduced glutamate turnover. The goal of this study was to use imaging of the human brain to investigate alterations in the glutamate signaling in cocaine addiction. Methods: Positron emission tomography imaging with the radiotracer [C-11]ABP688 was used to measure mGluR5 binding and magnetic resonance spectroscopy was used to measure glutamate-glutamine levels in the striatum of cocaine-addicted participants (n=15) compared with healthy control subjects (n=15). Following the scans, the cocaine-addicted volunteers performed cocaine self-administration sessions to investigate the correlation between cocaine-seeking behavior and mGluR5 receptor binding. Results: The results of the study showed that cocaine addiction was associated with a 20% to 22% reduction in [C-11]ABP688 binding in the striatum. A secondary analysis of cortical and subcortical regions other than the striatum showed a similar reduction in [C-11]ABP688 binding, suggesting that the decrease was widespread. No between-group differences were seen in the magnetic resonance spectroscopy measures of glutamate-glutamine in the left striatum. In addition, no correlation was seen between [C-11]ABP688 binding in the striatum and the choice to self-administer cocaine. Conclusions: Overall, these results show that long-term cocaine use is associated with a decrease in mGluR5 availability compared with matched healthy control subjects and suggests that this receptor may serve as a viable target for treatment development for this disorder.
引用
收藏
页码:165 / 171
页数:7
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