动物造模,药效评价 中国实验动物信息网 2024-10-30 1152

　　Objective To explore the effect of moderate intensity aerobic exercise on inhibitory Synaptic plasticity of VTA dopamine neurons in nicotine withdrawal mice, so as to provide some experimental evidence for reducing nicotine relapse by exercise.

　　Method: 8-week-old male C57BL/6 mice were randomly divided into saline quiet group (SS group), saline exercise group (SE group), nicotine quiet withdrawal group (NS group), and nicotine exercise withdrawal group (NE group). A mouse nicotine addiction model was established using a conditional position preference experiment. Afterwards, the administration was stopped, and the SE and NE groups of mice underwent continuous 2-week moderate intensity aerobic exercise intervention. The SS and NS groups of mice ate freely and were given water. Conditional positional preference experiment was used to detect nicotine relapse behavior in mice. The whole cell Patch clamp technique was used to record the spontaneous inhibitory postsynaptic current (sIPSC), minimal inhibitory postsynaptic current (mIPSC) and inhibitory postsynaptic current pairing pulse ratio (IPSC PPR) of VTA dopamine neurons. Detection of VTA using immunofluorescence staining γ- Expression of aminobutyrate limiting enzyme GAD67.

　　Result (1) The CPP score of the NS group was higher than that of the SS group, while the CPP score of the NE group was lower than that of the NS group; (2) The average frequency and amplitude of sIPSC in the NS group were higher than those in the SS group, while the average frequency and amplitude of sIPSC in the NE group were lower than those in the NS group; (3) The average frequency and amplitude of mIPSC in the NS group were higher than those in the SS group, while the average frequency and amplitude of mIPSC in the NE group were lower than those in the NS group; (4) At a stimulation interval of 20 ms and 50 ms, the IPSC PPR of the NS group was lower than that of the SS group, while the IPSC PPR of the NE group was higher than that of the NS group; (5) The expression of VTA GAD67 protein in the NS group was lower than that in the SS group, while the expression of VTA GAD67 protein in the NE group was higher than that in the NS group.

　　Conclusion: Two weeks of moderate intensity aerobic exercise reduces the presynaptic GABA release of dopamine neurons in the nicotine withdrawal model VTA, downregulates the number and/or function of postsynaptic GABAA receptors, and weakens inhibitory synaptic transmission efficiency. This may be one of the mechanisms by which aerobic exercise reduces nicotine relapse.