Tadmor Hagar, Golani Idit, Dvir Eshkar, Kremer Ilana, Shamir Alon
Psychobiology Research Laboratory, Mazor Mental Health Center, Akko, Israel; Faculty of Medicine in the Galilee, Bar-Ilan University, Zefat, Israel.
Department of Biotechnology, ORT Braude College, Karmiel, Israel.
Behav Brain Res. 2017 May 30;326:139-146. doi: 10.1016/j.bbr.2017.01.055. Epub 2017 Mar 8.
Adolescence is a critical period in brain development. During this critical period the seeking for hedonic activities is increased, and their activity signals are stronger than the regulatory signals of judgment and reasoning. We recently reported that alteration of ErbB signaling during this period led to elevated striatal dopamine levels and reduced preference for sweetness without affecting locomotor activity and exploratory behavior. In the current study, we extend our findings and explore whether inhibition of the ErbB pathway during adolescence or adulthood also affects alcohol preference (hedonic "liking"), avoidance learning, and motivational reward "wanting". We demonstrated that chronic administration of the pan-ErbB kinase inhibitor JNJ28871063 (JNJ) to adolescent mice, but not to adult mice, reduced alcohol preference compared with the saline-injected group, without affecting avoidance learning as measured by increasing concentrations of quinine in the bitter avoidance test. Adolescent JNJ-treated mice continue to demonstrate less alcohol preference in adulthood compared with their saline-injected controls. In addition, adolescent JNJ-treated mice and their saline-injected controls did not differ in the time they spent in the food-condition chamber, and in their preference for social odor. In contrast to adolescent JNJ- treated mice, blocking the pathway during adulthood alter the preference to natural reward. These data support our initial findings that interruption of the ErbB pathway during adolescence emerges in a reduced hedonic capacity that persists into adulthood, without disturbing avoidance and reward learning. In addition, this paper provides a further behavioral role of the ErbB signaling pathway in the reward system, and suggests a different time period for the involvement of the pathway in the "liking" and the "wanting" components of the system.
青春期是大脑发育的关键时期。在这个关键时期，对享乐活动的追求增加，且这些活动的信号强于判断和推理的调节信号。我们最近报道，在此期间ErbB信号的改变导致纹状体多巴胺水平升高，对甜味的偏好降低，而不影响运动活动和探索行为。在当前研究中，我们扩展了我们的发现，并探究在青春期或成年期抑制ErbB通路是否也会影响酒精偏好（享乐性“喜好”）、回避学习以及动机性奖励“渴望”。我们证明，对青春期小鼠而非成年小鼠长期给予泛ErbB激酶抑制剂JNJ28871063（JNJ），与注射生理盐水的组相比，降低了酒精偏好，且在苦味回避试验中通过增加奎宁浓度来测量时不影响回避学习。与注射生理盐水的对照相比，青春期接受JNJ治疗的小鼠在成年期仍表现出较低的酒精偏好。此外，青春期接受JNJ治疗的小鼠及其注射生理盐水的对照在食物条件室停留的时间以及对社交气味的偏好方面没有差异。与青春期接受JNJ治疗的小鼠不同，成年期阻断该通路会改变对自然奖励的偏好。这些数据支持了我们最初的发现，即在青春期中断ErbB通路会导致享乐能力降低，并持续到成年期，而不会干扰回避和奖励学习。此外，本文提供了ErbB信号通路在奖励系统中的进一步行为作用，并表明该通路参与奖励系统“喜好”和“渴望”成分的不同时间段。
