Reduced Nucleus Accumbens SK Channel Activity Enhances Alcohol Seeking during Abstinence

被引：80

作者：

Hopf, F. Woodward ^{[1
]}

Bowers, M. Scott ^{[1
]}

Chang, Shao-Ju ^{[1
]}

Chen, Billy T. ^{[1
]}

Martin, Miguel ^{[1
]}

Seif, Taban ^{[1
]}

Cho, Saemi L. ^{[1
]}

Tye, Kay ^{[1
]}

Bonci, Antonello ^{[1
,2
,3
,4
]}

机构：

[1] Univ Calif San Francisco, Ernest Gallo Clin & Res Ctr, San Francisco, CA 94608 USA

[2] Univ Calif San Francisco, Program Neurosci, San Francisco, CA 94608 USA

[3] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94608 USA

[4] Univ Calif San Francisco, Wheeler Ctr Neurobiol Addict, San Francisco, CA 94608 USA

来源：

NEURON | 2010年 / 65卷 / 05期

关键词：

CA2+-ACTIVATED K+ CHANNELS; COCAINE-SEEKING; ETHANOL-SEEKING; DRUG-ADDICTION; KAPPA-B; CALCIUM; RAT; MODULATION; DOPAMINE; NEURONS;

D O I：

10.1016/j.neuron.2010.02.015

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The cellular mechanisms underlying pathological alcohol seeking remain poorly understood. Here, we show an enhancement of nucleus accumbens (NAcb) core action potential firing ex vivo after protracted abstinence from alcohol but not sucrose self-ad ministration. Increased firing is associated with reduced small-conductance calcium-activated potassium channel (SK) currents and decreased SK3 but not SK2 subunit protein expression. Furthermore, SK activation ex vivo produces greater firing suppression in NAcb core neurons from alcohol-versus sucrose-abstinent rats. Accordingly, SK activation in the NAcb core significantly reduces alcohol but not sucrose seeking after abstinence. In contrast, NAcb shell and lateral dorsal striatal firing ex vivo are not altered after abstinence from alcohol, and SK activation in these regions has little effect on alcohol seeking. Thus, decreased NAcb core SK currents and increased excitability represents a critical mechanism that facilitates motivation to seek alcohol after abstinence.

引用

页码：682 / 694

页数：13

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