Increased habenular connectivity in opioid users is associated with an α5 subunit nicotinic receptor genetic variant.
Increased habenular connectivity in opioid users is associated with an α5 subunit nicotinic receptor genetic variant.
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DOI：
10.1111/ajad.12607
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发表时间：
2017-10
期刊：
影响因子：
--
通讯作者：
Salas R
中科院分区：
文献类型：
--
作者：
Curtis K;Viswanath H;Velasquez KM;Molfese DL;Harding MJ;Aramayo E;Baldwin PR;Ambrosi E;Madan A;Patriquin M;Frueh BC;Fowler JC;Kosten TR;Nielsen DA;Salas R
阿片类药物使用障碍（OUD）是一种基于对强化（渴望）和避免戒断的渴望而复发的慢性疾病。依赖和复发的令人厌恶的方面与一个叫做缰的小大脑结构有关，它表达大量阿片受体和烟碱受体。此外，阿片类药物戒断症状可以通过不仅阻断阿片类药物，而且阻断烟碱受体在阿片类药物治疗的啮齿动物中诱导。因此，这种受体共定位和戒断的交叉诱导可能导致烟碱受体的遗传变异，通过其对阿片类药物依赖的厌恶成分的影响来影响人类阿片类药物依赖的发展。我们研究了缰与相关脑结构，特别是纹状体的静息状态功能连接。我们比较了使用阿片类药物的戒断精神病患者（N=51）和不使用阿片类药物的精神病患者（N=254），以确定阿片类药物使用的内在表型，其重点是戒断回避和厌恶，而不是更常见的复发渴望方面。我们发现，缰核-纹状体连接在阿片类药物使用患者中更强。在具有低风险rs 16969968 GG基因型的阿片类药物使用患者中观察到缰核-纹状体连接增加，但在携带高风险AG或AA基因型的患者中未观察到。我们认为，缰核-纹状体功能连接的增加可能受到烟碱受体变体rs 16969968的调节，并可能导致阿片类药物使用的增加。我们的数据揭示了一个有希望的大脑靶点，用于开发新型抗成瘾疗法，并可能有助于开发针对阿片类药物滥用的个性化疗法。
Opioid use disorder (OUD) is a chronic disorder with relapse based on both desire for reinforcement (craving) and avoidance of withdrawal. The aversive aspect of dependence and relapse has been associated with a small brain structure called the habenula, which expresses large numbers of both opioid and nicotinic receptors. Additionally, opioid withdrawal symptoms can be induced in opioid-treated rodents by blocking not only opioid, but also nicotinic receptors. This receptor co-localization and cross-induction of withdrawal therefore might lead to genetic variation in the nicotinic receptor influencing development of human opioid dependence through its impact on the aversive components of opioid dependence. We studied habenular resting state functional connectivity with related brain structures, specifically the striatum. We compared abstinent psychiatric patients who use opioids (N=51) to psychiatric patients who don’t (N=254) to identify an endophenotype of opioid use that focused on withdrawal avoidance and aversion rather than the more commonly examined craving aspects of relapse. We found that habenula – striatal connectivity was stronger in opioid-using patients. Increased habenula-striatum connectivity was observed in opioid-using patients with the low risk rs16969968 GG genotype, but not in patients carrying the high risk AG or AA genotypes. We propose that increased habenula – striatum functional connectivity may be modulated by the nicotinic receptor variant rs16969968 and may lead to increased opioid use. Our data uncovered a promising brain target for development of novel anti-addiction therapies and may help the development of personalized therapies against opioid abuse.
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影响因子：
4.8
作者：
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通讯作者：
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影响因子：
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影响因子：
3.6
作者：
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