p75NTR Regulates Morphine-induced CPP and Related mRNA Expression in Adolescent Mice through Trk Dependent Pathway

Abstract Drug abuses in adolescents have become a major public health concern, and one of the major abusive drugs is morphine. p75NTR is an age-related receptor that can mediate synaptic plasticity in the hippocampus. Previous studies also show that its signaling pathway is involved in some drug-taking behaviors. Using morphine-induced conditioned place preference (CPP) of mice, the present study aims to analyze changes of p75NTR in the hippocampus. As the expression and function of p75NTR can be regulated by the activities of Trk receptors, we also aim to detect whether the activation of Trk can regulate changes in expressions of p75NTR and acquisitions of morphine-induced CPP. Our results show that the expression of p75NTR in the hippocampus is significantly increased in the morphine-induced CPP of adolescent mice, but not in that of adult mice. It can be explained by that the p75NTR plays a more important role in the brains of adolescent mice. We also find a Trk phosphorylation inhibitor, K252a, can reduce the preference values of CPP in adolescent mice, as well as attenuating the mRNA expression of p75NTR and its downstream molecular, CDC42, in the hippocampus of adolescent mice. The present study suggests that the p75NTR may be an age-related regulator of morphine abuse, and its function may be regulated by the activity of Trk.