Effects And Mechanism Of Con-G Analogues On Striatum Neurons Apoptosis In Morphine Dependence Mice

1 Purpose:We approached the possible mechanism of morphine dependence from the perspective of neuronal apoptosis, then evaluated the intervention effect of Con-G and analogues on morphine physical dependence.2 Methods:After establishing morphine induced conditioned place preference and physical dependence model, transmission electron microscopy and western blotting were used to detect the apoptosis and the changes of the levels of related proteins.3 Results:1. In the CPP acquisition and reinstatement phases, striatal neurons karyopyknosis deformation, chromatin margination, the electron density increased. In the CPP extinction phase, striatal neurons appeared normal, uniform electron density; abnormal lysosome scattered.2. In the CPP acquisition, extinction and reinstatement phases, larger amounts and more intensive shaft-shaft synapses, the axon-dendrite synapses appeared in striatum.3. In the CPP acquisition, extinction and reinstatement phases, the relative protein levels of Procaspase3 were no difference between saline group mice and morphine mice in Hp and PFC. But in stratum, in the CPP acquisition and reinstatement phases, the relative protein levels of Procaspase3 decreased.4.150,300,600pmolGlu-Con-G and Glu-Con-G[1-13] can inhibit the naloxone-induced jumping behavior in a dose-effect dependent manner.150,300,600pmolGlu-Con-G and 150,600pmol Glu-Con-G[1-13] can inhibit the naloxone-induced body weight loss.5.150,300,600pmolGlu-Con-G and Glu-Con-G[1-13] significantly increased the level of Procaspase3 in striatum in morphine induced physical dependence mice.4 Conclusions:1. In the CPP acquisition phase, there was apoptosis in striatum brain region; in the CPP extinction phase, there were no significant abnormalities, but abnormal lysosome. In the CPP reinstatement phase, it appeared apoptosis.2. Long-term morphine treatment increased the number of synapses, dendrites, axons more intensive. It can also decrease the levels of Procaspase3.3. Glu-Con-G,Glu-Con-G[1-13] can inhibit morphine-induced mice physical dependence. They can also significantly increase the level of Procaspase3 in striatum.