Role of Specific Synaptic Plasticity Interfering Peptides in the Expression of Morphine Induced Conditioned Place Preference in Mice

特异突触可塑性干扰肽在小鼠吗啡条件化位置偏爱表达过程中的作用(英文)

Learned association between context and drug abuse is essential for the drug conditioned place preference （CPP）, which is an animal model widely used to measure drug reward. Synaptic plasticity, in the form of long-term potentiation （LTP） and depression （LTD）, is regarded as a proposed cellular substrate of learning and memory. However, the exact role of LTP/LTD in addiction is not known yet. Therefore, by bioinformatics we designed peptides aiming to interfere with LTP and LTD respectively, to study their individual role in the expression of morphine CPP. We found that the interfering peptide Pep-A2 can specifically block hippocampal LTP in CA1 region, whereas Pep-A3 can block LTD in this region. Treatment of either of their cell penetrating forms （Tat-A2 or Tat-A3） before test can block the expression of Morphine CPP in mice. These results suggested that both LTP and LTD are required in the drug-associated learning and memory.

在作为成瘾检测手段的条件化位置偏爱模型中,环境背景和成瘾药物间的关联性学习起着关键的作用。突触可塑性作为学习记忆可能的物质基础,在药物成瘾方面的研究也越来越多,但其表现形式,长时程增强(LTP)或者长时程抑制(LTD)在成瘾过程中所发挥的具体作用尚不得而知。因此,本文利用生物信息学手段,设计并合成了旨在分别阻断LTP和LTD的干扰肽,研究其对小鼠吗啡条件化位置偏爱的影响。结果发现,干扰肽Pep-A2和Pep-A3能够分别特异地阻断海马CA1区的LTP和LTD,在测试前尾静脉注射具有穿膜特性的LTP/LTD特异性干扰肽(Tat-A2/Tat-A3),均能阻断或损伤吗啡诱导的条件化位置偏爱的表达。此发现提示我们,LTP和LTD在成瘾性异常记忆的过程中均发挥着重要的作用。