Oxytocin Acts in Nucleus Accumbens to Attenuate Methamphetamine Seeking and Demand.
Oxytocin Acts in Nucleus Accumbens to Attenuate Methamphetamine Seeking and Demand.
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DOI：
10.1016/j.biopsych.2016.11.011
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发表时间：
2017-06-01
影响因子：
10.6
通讯作者：
Aston-Jones G
中科院分区：
文献类型：
--
作者：
Cox BM;Bentzley BS;Regen-Tuero H;See RE;Reichel CM;Aston-Jones G
有证据表明，催产素是一种内源性多肽，因其在社会行为、分娩和哺乳中的作用而闻名，是一种有前途的成瘾药物治疗方法。我们采用了一种大鼠的会话内行为经济学(BE)程序来检验催产素作为甲基苯丙胺(冰毒)成瘾的药物疗法。BE范式是以BE程序为模型，用于评估人类吸毒者的毒品动机。重要的是，跨物种评估的相同BE变量已被证明可以预测以后的复发行为。因此，临床前BE研究的翻译潜力特别大。我们测试了全身注射催产素和微量注射催产素对自我静脉注射需求的影响。使用行为经济学范式在雄性和雌性大鼠中消除和恢复冰毒搜索。评估了冰毒需求和冰毒寻觅之间的相关性。与男性相比，女性对冰毒的需求(即动机)更大。在男性和女性中，冰毒需求预示着冰毒寻求的恢复，而全身催产素减少了对冰毒的需求，削弱了对冰毒搜索的恢复。催产素在减少毒品动机最强的大鼠的冰毒需求和寻找方面最有效。最后，我们发现，全身性催产素的这些作用是通过伏核(NAC)的作用来调节的。催产素减少了男女对冰毒的需求和寻找，这些作用依赖于NAC中的催产素信号。总体而言，这些数据表明，开发基于催产素的疗法可能是治疗人类冰毒成瘾的一种有前途的方法。
Evidence indicates that oxytocin, an endogenous peptide well known for its role in social behaviors, childbirth and lactation, is a promising addiction pharmacotherapy. We employed a within-session behavioral-economic (BE) procedure in rats to examine oxytocin as a pharmacotherapy for methamphetamine (meth) addiction. The BE paradigm was modeled after BE procedures used to assess motivation for drugs in human addicts. Importantly, the same BE variables assessed across species have been shown to predict later relapse behavior. Thus, the translational potential of preclinical BE studies is particularly strong. We tested the effects of systemic and microinfused oxytocin on demand for self-administered i.v. meth and reinstatement of extinguished meth-seeking in male and female rats using a behavioral economics paradigm. Correlations between meth demand and meth seeking were assessed. Females showed greater demand (i.e., motivation) for meth compared to males. In both males and females, meth demand predicted reinstatement of meth-seeking, and systemic oxytocin decreased demand for meth and attenuated reinstatement to meth seeking. Oxytocin was most effective at decreasing meth demand and seeking in rats with the strongest motivation for drug. Finally, we found that these effects of systemic oxytocin were mediated by actions in the nucleus accumbens (NAc). Oxytocin decreases meth demand and seeking in both sexes, and these effects depend on oxytocin signaling in the NAc. Overall, these data indicate that development of oxytocin-based therapies may be a promising treatment approach for meth addiction in humans.