Transition to Addiction Is Associated with a Persistent Impairment in Synaptic Plasticity

被引：283

作者：

Kasanetz, Fernando ^{[1
,2
]}

Deroche-Gamonet, Veronique ^{[1
,2
]}

Berson, Nadege ^{[1
,2
]}

Balado, Eric ^{[1
,2
]}

Lafourcade, Mathieu ^{[1
,2
]}

Manzoni, Olivier ^{[1
,2
]}

Piazza, Pier Vincenzo ^{[1
,2
]}

机构：

[1] INSERM, U862, NeuroCtr Magendie, F-33077 Bordeaux, France

[2] Univ Bordeaux, F-33077 Bordeaux, France

来源：

SCIENCE | 2010年 / 328卷 / 5986期

关键词：

LONG-TERM DEPRESSION; DRUG-SEEKING; COCAINE ADDICTION; NEURAL MECHANISMS; NUCLEUS-ACCUMBENS; BEHAVIOR; LTD; VTA;

D O I：

10.1126/science.1187801

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Chronic exposure to drugs of abuse induces countless modifications in brain physiology. However, the neurobiological adaptations specifically associated with the transition to addiction are unknown. Cocaine self-administration rapidly suppresses long-term depression (LTD), an important form of synaptic plasticity in the nucleus accumbens. Using a rat model of addiction, we found that animals that progressively develop the behavioral hallmarks of addiction have permanently impaired LTD, whereas LTD is progressively recovered in nonaddicted rats maintaining a controlled drug intake. By making drug seeking consistently resistant to modulation by environmental contingencies and consequently more and more inflexible, a persistently impaired LTD could mediate the transition to addiction.

引用

页码：1709 / 1712

页数：4

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