Role of NMDA receptors in dopamine neurons for plasticity and addictive behaviors

被引：164

作者：

Zweifel, Larry S. ^{[1
,2
]}

Argilli, Emanuela ^{[3
,4
]}

Bonci, Antonello ^{[3
,4
]}

Palmiter, Richard D. ^{[1
,2
]}

机构：

[1] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA

[2] Univ Washington, Dept Biochem, Seattle, WA 98195 USA

[3] Univ Calif San Francisco, Ernest Gallo Clin & Res Ctr, San Francisco, CA 94110 USA

[4] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94110 USA

来源：

NEURON | 2008年 / 59卷 / 03期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/j.neuron.2008.05.028

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

A single exposure to drugs of abuse produces an NMDA receptor (NMDAR)-dependent long-term potentiation (LTP) of AMPA receptor (AMPAR) currents in DA neurons; however, the importance of LTP for various aspects of drug addiction is unclear. To test the role of NMDAR-dependent plasticity in addictive behavior, we genetically inactivated functional NMDAR signaling exclusively in DA neurons (KO mice). Inactivation of NMDARs results in increased AMPAR-mediated transmission that is indistinguishable from the increases associated with a single cocaine exposure, yet locomotor responses to multiple drugs of abuse were unaltered in the KO mice. The initial phase of locomotor sensitization to cocaine is intact; however, the delayed sensitization that occurs with prolonged cocaine withdrawal did not occur. Conditioned behavioral responses for cocaine-testing environment were also absent in the KO mice. These findings provide evidence for a role of NMDAR signaling in DA neurons for specific behavioral modifications associated with drug seeking behaviors.

引用

页码：486 / 496

页数：11