Protracted withdrawal from alcohol and drugs of abuse impairs long-term potentiation of intrinsic excitability in the juxtacapsular bed nucleus of the stria terminalis.
Protracted withdrawal from alcohol and drugs of abuse impairs long-term potentiation of intrinsic excitability in the juxtacapsular bed nucleus of the stria terminalis.
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DOI：
10.1523/jneurosci.5129-08.2009
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发表时间：
2009-04-29
期刊：
影响因子：
--
通讯作者：
Sanna PP
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文献类型：
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作者：
Francesconi W;Berton F;Repunte-Canonigo V;Hagihara K;Thurbon D;Lekic D;Specio SE;Greenwell TN;Chen SA;Rice KC;Richardson HN;O'Dell LE;Zorrilla EP;Morales M;Koob GF;Sanna PP
基底外侧杏仁核（BLA）通过终纹传入后，基底外侧BNST（jcBNST）被激活，并投射回前BLA和杏仁核中央核（CeA）。在这里，我们显示了一种形式的长期增强的内在兴奋性（LTP-IE）的jcBNST神经元的高频刺激（HFS）的终纹。这LTP-IE，其特征在于在发射阈值和增加的时间保真度的减少，在长期的自我管理的酒精，可卡因和海洛因的戒断过程中受损。这种损害是分级的，并且在自我施用足以维持依赖性的药物量的大鼠中更明显。CRF系统的失调与长期戒断依赖性药物使用的表现有关。给予选择性促肾上腺皮质激素释放因子受体1（CRF 1）拮抗剂R121919，但不给予CRF 2拮抗剂astressin 2-B（A2-B），使有酒精依赖史的动物的jcBNST LTP-IE正常化;重复但非急性给予CRF本身可降低jcBNST LTP-IE。因此，慢性激活的CRF系统介导的jcBNST神经元的整合特性的变化可能有助于持久的情绪失调与长期戒断。
The juxtacapsular BNST (jcBNST) is activated in response to basolateral amygdala (BLA) inputs through the stria terminalis and projects back to the anterior BLA and to the central nucleus of the amygdala (CeA). Here we show a form of long-term potentiation of the intrinsic excitability (LTP-IE) of jcBNST neurons in response to high-frequency stimulation (HFS) of the stria terminalis. This LTP-IE, which was characterized by a decrease in the firing threshold and increased temporal fidelity of firing, was impaired during protracted withdrawal from self-administration of alcohol, cocaine, and heroin. Such impairment was graded and was more pronounced in rats that self-administered amounts of the drugs sufficient to maintain dependence. Dysregulation of the CRF system has been implicated in manifestation of protracted withdrawal from dependent drug use. Administration of the selective corticotropin-releasing factor receptor 1 (CRF1) antagonist R121919, but not of the CRF2 antagonist astressin2-B (A2-B), normalized jcBNST LTP-IE in animals with a history of alcohol dependence; repeated, but not acute, administration of CRF itself produced a decreased jcBNST LTP-IE. Thus, changes in the integration properties of jcBNST neurons mediated by chronic activation of the CRF system may contribute to the persistent emotional dysregulation associated with protracted withdrawal.