β1 Adrenergic receptors in the bed nucleus of stria terminalis mediate differential responses to opiate withdrawal
β1 Adrenergic receptors in the bed nucleus of stria terminalis mediate differential responses to opiate withdrawal
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DOI：
10.1038/sj.npp.1301140
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发表时间：
2007-03-01
影响因子：
7.6
通讯作者：
Akil, Huda
中科院分区：
文献类型：
--
作者：
Cecchi, Marco;Capriles, Nancy;Akil, Huda
阿片类戒断的负面身体和情感方面有助于延长药物滥用。戒断治疗仅在一部分受试者中成功，但对这些个体差异的神经生物学原因知之甚少。在这里，我们比较了阿片类药物戒断的躯体和动机成分的动物与高反应性（HR）与低反应性（LR）的新奇性，与药物滥用的差异脆弱性相关的表型。在戒断期间，HR相对于LR表现出牙齿抖动和眼颤发作增加，这是与肾上腺素能调节相关的躯体体征。鉴于阿片类药物戒断延长杏仁核的去甲肾上腺素能回路的作用，我们研究了肾上腺素能受体基因表达的床核的终纹（BST）和中央核的杏仁核。相对于LR，HR大鼠在外侧和内侧BST中表现出β（1）肾上腺素能受体表达的选择性增加。为了揭示这种差异的功能相关性，我们将一种选择性β 1受体拮抗剂倍他洛尔微量注射到背侧BST中，并评估戒断期间的躯体和情感反应。倍他洛尔微量注射以剂量依赖性方式将HR中的牙齿抖动事件降低至LR动物中观察到的水平。此外，拮抗剂阻断条件性位置厌恶，一个措施的负面影响与撤回，在HR，但不是在LR动物。我们的研究结果首次揭示了新颖性的反应预测阿片类药物依赖的躯体和情感方面，BST中的b1受体与阿片类药物戒断有关，但仅限于寻求新奇的个体。
The negative physical and affective aspects of opioid abstinence contribute to the prolongation of substance abuse. Withdrawal treatment is successful only in a subset of subjects, yet little is known about the neurobiological causes of these individual differences. Here, we compare the somatic and motivational components of opioid withdrawal in animals with high reactivity ( HR) vs low reactivity ( LR) to novelty, a phenotype associated with differential vulnerability to drug abuse. During withdrawal, HR relative to LR showed increased teeth chattering and eye twitching episodes, somatic signs associated with adrenergic modulation. Given the role of noradrenergic circuitry of the extended amygdala in opioid withdrawal, we examined adrenergic receptor gene expression in the bed nucleus of stria terminalis ( BST) and central nucleus of the amygdala. Relative to LR, HR rats exhibit a selective increase in beta(1) adrenergic receptor expression in lateral and medial BST. To uncover the functional relevance of this difference, we microinjected betaxolol, a selective beta(1) receptor antagonist, into dorsal BST and assessed somatic and affective responses during withdrawal. Betaxolol microinjection dose-dependently decreased teeth chattering episodes in HR to levels observed in LR animals. Moreover, the antagonist blocked conditioned place aversion, a measure of negative affect associated with withdrawal, in HR but not in LR animals. Our results reveal for the first time that reactivity to novelty predicts somatic and affective aspects of opiate dependence, and that b1 receptors in BST are implicated in opiate withdrawal but only in novelty-seeking individuals.