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

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 memor