Huff Mary L, LaLumiere Ryan T
Department of Psychology, University of Iowa, Iowa City, IA, USA.
1] Department of Psychology, University of Iowa, Iowa City, IA, USA [2] Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, IA, USA.
Neuropsychopharmacology. 2015 Mar;40(4):861-73. doi: 10.1038/npp.2014.260. Epub 2014 Sep 26.
Recent findings suggest that the mesolimbic dopamine neurons, known to promote cocaine-seeking behavior, are strongly inhibited by a newly characterized region of the midbrain known as the rostromedial tegmental nucleus (RMTg). The RMTg appears to be involved in generating reward-prediction error signals and inhibition of motivated behaviors, suggesting its potential involvement in the extinction of cocaine seeking as well. Therefore, to address this question, male Sprague-Dawley rats underwent surgeries for implantation of catheters and cannulas targeted at the RMTg. After cocaine self-administration, rats underwent modified extinction training. Pre- or post-training intra-RMTg microinjections of the allosteric AMPA receptor potentiator PEPA during the first 5 days of extinction training appeared to enhance the retention of the extinction learning. Following the extinction training, rats underwent cue-induced reinstatement or an 'inactivation-alone' extinction tests. RMTg inactivation before a cue-induced reinstatement session or inactivation alone before a standard extinction session increased overall lever pressing. To determine whether these effects generalized to other motivated behaviors, additional experiments examining food-seeking behavior were also conducted. The results from the food-seeking experiments indicate that PEPA microinjections into the RMTg did not influence the extinction of food seeking and that, at least in rats that had not been given PEPA during the extinction learning experiments, RMTg inactivation had no effect on lever pressing during the cue-induced reinstatement or inactivation-alone tests. These findings suggest that the RMTg provides general behavioral inhibition and is potentially involved in learning to extinguish cocaine-seeking behavior in rats.
最近的研究结果表明，已知会促进觅可卡因行为的中脑边缘多巴胺神经元，受到中脑一个新发现的区域——嘴内侧被盖核（RMTg）的强烈抑制。RMTg似乎参与产生奖励预测误差信号并抑制动机行为，这表明它也可能参与可卡因觅求行为的消退。因此，为了解决这个问题，雄性斯普拉格-道利大鼠接受了手术，在其RMTg植入导管和插管。在可卡因自我给药后，大鼠接受了改良的消退训练。在消退训练的前5天，在RMTg内进行变构AMPA受体增强剂PEPA的训练前或训练后微量注射，似乎能增强消退学习的记忆保持。在消退训练后，大鼠接受线索诱导的复吸或“仅失活”消退测试。在线索诱导的复吸环节之前使RMTg失活，或在标准消退环节之前单独使RMTg失活，都会增加总的杠杆按压次数。为了确定这些效应是否适用于其他动机行为，还进行了额外的实验来研究觅食行为。觅食实验的结果表明，向RMTg内微量注射PEPA不会影响觅食行为的消退，并且，至少在消退学习实验中未给予PEPA的大鼠中，RMTg失活在线索诱导的复吸或仅失活测试期间对杠杆按压没有影响。这些发现表明，RMTg提供一般性的行为抑制，并且可能参与大鼠可卡因觅求行为消退的学习过程。
