Glutamate receptors on dopamine neurons control the persistence of cocaine seeking

被引：183

作者：

Engblom, David ^{[2
]}

Bilbao, Ainhoa ^{[3
]}

Sanchis-Segura, Carles ^{[3
]}

Dahan, Lionel ^{[1
]}

Perreau-Lenz, Stephanie ^{[3
]}

Balland, Benedicte ^{[1
]}

Parkitna, Jan Rodriguez ^{[2
]}

Lujan, Rafael ^{[5
]}

Halbout, Briac ^{[3
]}

Mameli, Manuel ^{[1
]}

Parlato, Rosanna ^{[2
]}

Sprengel, Rolf ^{[6
]}

Luescher, Christian ^{[1
,4
]}

Schuetz, Guenther ^{[2
]}

Spanagel, Rainer ^{[3
]}

机构：

[1] Univ Geneva, Fac Med, Dept Basic Neurosci, CH-1211 Geneva, Switzerland

[2] German Canc Res Ctr, Div Mol Biol Cell 1, D-69120 Heidelberg, Germany

[3] Cent Inst Mental Hlth, Dept Psychopharmacol, D-68159 Mannheim, Germany

[4] Univ Hosp Geneva, Dept Clin Neurosci, Neurol Clin, CH-1211 Geneva, Switzerland

[5] Univ Castilla La Mancha, Dept Ciencias Med, Fac Med CRIB, Albacete 02006, Spain

[6] Max Planck Inst Med Res, Dept Mol Neurosci, D-69120 Heidelberg, Germany

来源：

NEURON | 2008年 / 59卷 / 03期

基金：

瑞典研究理事会;

关键词：

D O I：

10.1016/j.neuron.2008.07.010

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Cocaine strengthens excitatory synapses onto midbrain dopamine neurons through the synaptic delivery of GluR1-containing AMPA receptors. This cocaine-evoked plasticity depends on NMDA receptor activation, but its behavioral significance in the context of addiction remains elusive. Here, we generated mice lacking the GluR1, GluR2, or NR1 receptor subunits selectively in dopamine neurons. We report that in midbrain slices of cocaine-treated mice, synaptic transmission was no longer strengthened when GluR1 or NR1 was abolished, while in the respective mice the drug still induced normal conditioned place preference and locomotor sensitization. In contrast, extinction of drug-seeking behavior was absent in mice lacking GluR1, while in the NR1 mutant mice reinstatement was abolished. In conclusion, cocaine-evoked synaptic plasticity does not mediate concurrent short-term behavioral effects of the drug but may initiate adaptive changes eventually leading to the persistence of drug-seeking behavior.

引用

页码：497 / 508

页数：12

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