Cox Brittney M, Bentzley Brandon S, Regen-Tuero Helaina, See Ronald E, Reichel Carmela M, Aston-Jones Gary
Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina.
Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina.
Biol Psychiatry. 2017 Jun 1;81(11):949-958. doi: 10.1016/j.biopsych.2016.11.011. Epub 2016 Dec 1.
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 humans with addiction. 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 intravenous meth and reinstatement of extinguished meth seeking in male and female rats using a BE paradigm. Correlations between meth demand and meth seeking were assessed.
Female rats showed greater demand (i.e., motivation) for meth compared with male rats. In both male and female rats, 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, these effects of systemic oxytocin were mediated by actions in the nucleus accumbens.
Oxytocin decreases meth demand and seeking in both sexes, and these effects depend on oxytocin signaling in the nucleus accumbens. Overall, these data indicate that development of oxytocin-based therapies may be a promising treatment approach for meth addiction in humans.
有证据表明，催产素作为一种以内分泌肽形式存在，在社会行为、分娩和泌乳中发挥作用而闻名，是一种很有前景的成瘾药物疗法。我们采用大鼠在实验期间的行为经济学（BE）程序，来研究催产素作为甲基苯丙胺（冰毒）成瘾的药物疗法。BE范式是模仿用于评估成瘾人类对药物动机的BE程序建立的。已证明跨物种评估的相同BE变量可预测后期的复发行为。因此，临床前BE研究的转化潜力尤为强大。
我们使用BE范式测试了全身和微量注射催产素对雄性和雌性大鼠自我注射静脉冰毒的需求以及恢复已消退的觅药行为的影响。评估了冰毒需求与觅药行为之间的相关性。
与雄性大鼠相比，雌性大鼠对冰毒的需求（即动机）更大。在雄性和雌性大鼠中，冰毒需求都可预测觅药行为的恢复，全身注射催产素可降低对冰毒的需求，并减弱对觅药行为的恢复。催产素在降低对冰毒需求和觅药行为方面，对药物动机最强的大鼠最为有效。最后，全身注射催产素的这些作用是由伏隔核中的作用介导的。
催产素可降低两性对冰毒的需求和觅药行为，且这些作用取决于伏隔核中的催产素信号传导。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景的治疗方法。
