Repeated exposure to methamphetamine causes long-lasting presynaptic corticostriatal depression that is renormalized with drug read ministration

被引：78

作者：

Bamford, Nigel S. ^{[1
,2
,3
,4
]}

Zhang, Hui ^{[5
,6
]}

Joyce, John A. ^{[1
]}

Scarlis, Christine A. ^{[1
]}

Hanan, Whitney ^{[1
]}

Wu, Nan-Ping ^{[7
]}

Andre, Veronique M. ^{[7
]}

Cohen, Rachel ^{[7
]}

Cepeda, Carlos ^{[7
]}

Levine, Michael S. ^{[7
]}

Harleton, Erin ^{[5
,6
]}

Sulzer, David ^{[5
,6
,8
,9
]}

机构：

[1] Univ Washington, Dept Neurol, Seattle, WA 98105 USA

[2] Univ Washington, Ctr Human Dev & Disabil, Seattle, WA 98105 USA

[3] Univ Washington, Dept Pediat & Psychol, Seattle, WA 98105 USA

[4] Childrens Hosp & Reg Med Ctr, Seattle, WA 98105 USA

[5] Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA

[6] Columbia Univ Coll Phys & Surg, Dept Pharmacol & Psychiat, New York, NY 10032 USA

[7] Univ Calif Los Angeles, David Geffen Sch Med, Mental Retardat Res Ctr, Los Angeles, CA 90095 USA

[8] Columbia Univ Coll Phys & Surg, Ctr Neurobiol & Behav, New York, NY 10032 USA

[9] New York State Psychiat Inst & Hosp, Div Mol Therapeut, New York, NY 10032 USA

来源：

NEURON | 2008年 / 58卷 / 01期

关键词：

D O I：

10.1016/j.neuron.2008.01.033

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Addiction-associated behaviors such as drug craving and relapse are hypothesized to result from synaptic changes that persist long after withdrawal and are renormalized by drug reinstatement, although such chronic synaptic effects have not been identified. We report that exposure to the dopamine releaser methamphetamine for 10 days elicits a long-lasting (>4 rnonth) depression at corticostriatal terminals that is reversed by methamphetamine readministration. Both methamphetamine-induced chronic presynaptic depression and the drug's selective renormalization in drug-experienced animals are independent of corresponding long-term changes in synaptic dopamine release but are due to alterations in D1 dopamine and cholinergic receptor systems. These mechanisms might provide a synaptic basis that underlies addiction and habit learning and their long-term maintenance.

引用

页码：89 / 103

页数：15

共 48 条

[1]

Abercrombie ED, 1997, J NEUROSCI, V17, P8498

[2] Transition to drug addiction: a negative reinforcement model based on an allostatic decrease in reward function [J].