Orexin-Corticotropin-Releasing Factor Receptor Heteromers in the Ventral Tegmental Area as Targets for Cocaine

被引：51
|
作者：
Navarro, Gemma [1 ,2 ]
Quiroz, Cesar [3 ]
Moreno-Delgado, David [1 ,2 ]
Sierakowiak, Adam [3 ]
McDowell, Kimberly [3 ]
Moreno, Estefania [1 ,2 ]
Rea, William [3 ]
Cai, Ning-Sheng [3 ]
Aguinaga, David [1 ,2 ]
Howell, Lesley A. [4 ]
Hausch, Felix [5 ]
Cortes, Antonio [1 ,2 ]
Mallol, Josefa [1 ,2 ]
Casado, Vicent [1 ,2 ]
Lluis, Carme [1 ,2 ]
Canela, Enric I. [1 ,2 ]
Ferre, Sergi [3 ]
McCormick, Peter J. [1 ,2 ,4 ]
机构：
[1] Univ Barcelona, Fac Biol, Ctr Biomed Res Neurodegenerat Dis Network, Dept Biochem & Mol Biol, E-08028 Barcelona, Spain
[2] Univ Barcelona, Inst Biomed, E-08028 Barcelona, Spain
[3] Natl Inst Drug Abuse, Integrat Neurobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA
[4] Univ E Anglia, Sch Pharm, Norwich NR4 7TJ, Norfolk, England
[5] Max Planck Inst Psychiat, D-80804 Munich, Germany
来源：
JOURNAL OF NEUROSCIENCE | 2015年 / 35卷 / 17期
关键词：
cocaine; CRF receptor; GPCR heteromer; orexin receptor; sigma receptor; STRESS-INDUCED RELAPSE; PROTEIN-COUPLED RECEPTORS; CRF-BINDING-PROTEIN; SIGMA-1; RECEPTORS; DOPAMINE NEURONS; INDUCED REINSTATEMENT; DRUG SEEKING; OREXIN/HYPOCRETIN; HYPOTHALAMUS; PHARMACOLOGY;
D O I：
10.1523/JNEUROSCI.4364-14.2015
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Release of the neuropeptides corticotropin-releasing factor (CRF) and orexin-A in the ventral tegmental area (VTA) play an important role in stress-induced cocaine-seeking behavior. We provide evidence for pharmacologically significant interactions between CRF and orexin-A that depend on oligomerization of CRF1 receptor (CRF1R) and orexin OX1 receptors (OX1R). CRF1R-OX1R heteromers are the conduits of a negative crosstalk between orexin-A and CRF as demonstrated in transfected cells and rat VTA, in which they significantly modulate dendritic dopamine release. The cocaine target sigma(1) receptor (sigma R-1) also associates with the CRF1R-OX1R heteromer. Cocaine binding to the sigma R-1-CRF1R-OX1R complex promotes a long-term disruption of the orexin-A-CRF negative crosstalk. Through this mechanism, cocaine sensitizes VTA cells to the excitatory effects of both CRF and orexin-A, thus providing a mechanism by which stress induces cocaine seeking.
引用
收藏
页码：6639 / 6653
页数：15
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