Oxytocin Reduces Alcohol Cue-Reactivity in Alcohol-Dependent Rats and Humans
Oxytocin Reduces Alcohol Cue-Reactivity in Alcohol-Dependent Rats and Humans
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DOI：
10.1038/npp.2017.257
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发表时间：
2018-05-01
影响因子：
7.6
通讯作者：
Spanagel, Rainer
中科院分区：
文献类型：
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作者：
Hansson, Anita C.;Koopmann, Anne;Spanagel, Rainer
经批准的酒精使用障碍药物治疗的有效性有限，因此有必要开发易于转化为临床的新药。催产素就是其中之一，因为它能与几种酒精引起的效应相互作用。通过qRT-PCR、原位杂交、受体放射自显影（[（125）l]OVTA结合）和免疫组织化学分析酒精依赖大鼠以及人类酒精成瘾者和对照的死后脑中催产素系统的表达。酒精自我管理和线索诱导的恢复行为后，测定脑室内注射10 nM催产素依赖大鼠。在这里，我们显示了一个明显的上调催产素受体在酒精依赖大鼠和已故酗酒者的脑组织，主要是在额叶和纹状体区。这种上调最有可能源于下丘脑核中催产素表达的减少。药理学验证表明，催产素减少依赖性大鼠的线索诱导的恢复反应，而在非依赖性大鼠中没有观察到这种作用。最后，一项临床试验研究（德国临床试验编号DRKS 00009253）在重度社交男性饮酒者中使用功能性磁共振成像显示，鼻内催产素（24 IU）降低了大脑网络中的神经线索反应性，这与在依赖性大鼠和人类中检测到的催产素受体表达增加相似。这些研究表明，催产素可能被用作一种抗痉挛药物，从而可能对酗酒者的治疗结果产生积极影响。
Approved pharmacological treatments for alcohol use disorder are limited in their effectiveness, and new drugs that can easily be translated into the clinic are warranted. One of those candidates is oxytocin because of its interaction with several alcohol-induced effects. Alcoholdependent rats as well as post-mortem brains of human alcoholics and controls were analyzed for the expression of the oxytocin system by qRT-PCR, in situ hybridizaton, receptor autoradiography ([(125)l]OVTA binding), and immunohistochemistry. Alcohol self administration and cue-induced reinstatement behavior was measured after intracerebroventicular injection of 10 nM oxytocin in dependent rats. Here we show a pronounced upregulation of oxytocin receptors in brain tissues of alcohol dependent rats and deceased alcoholics, primarily in frontal and striatal areas. This upregulation stems most likely from reduced oxytocin expression in hypothalamic nuclei. Pharmacological validaton showed that oxytocin reduced cue-induced reinstatement response in dependent rats-an effect that was not observed in nondependent rats. Finally, a clinical pilot study (German clinical trial number DRKS00009253) using functional magnetic resonance imaging in heavy social male drinkers showed that intranasal oxytocin (24 IU) decreased neural cue-reactivity in brain networks similar to those detected in dependent rats and humans with increased oxytocin receptor expression. These studies suggest that oxytocin might be used as an anticraving medication and thus may positvely affect treatment outcomes in alcoholics.