A Study Of VTA's Plasticity And Dopamine Neurons Membrane Current Mediated By NMDA Receptor In The VTA On Heroin-addicted Rats

Objective:To examine the synapse plasticity changes in the VTA as well as its dopamine neurons membrane current mediated by NMDA receptor in heroin-addicted rats.Methods:80 male Sprague-Dawley rats (180-220 g) were randomly divided into the following 3 groups:control group rats were intraperiatoneal injected with 0.2 ml saline; heroin-treated group rats were injected subcutaneously twice a day according to the principle of daily increasing dose(first day inject 3mg/kg and the dose of 9d was 27mg/kg), abstinence group rats were intraperiatoneal injected naloxone on the tenth day. On the tenth day the withdrawal symptoms precipitated by intraperitoneal injection of naloxone were evaluated and the heroin-addicted model was established. The control group was inject the equivalent volume of saline. After the model was established, heroin was injected continuously according to the maintenance dose(27mg/kg per day) in heroin-addicted group. Population spike was recorded in vivo by stimulate the VTA and nucleus accumbens circuit, for the induction of LTP, high-frequency stimulations were applied to this circuit. Take TH-immunohistochemistry to mark the dopamine neurons and use brain slice patch-clamp technique to record the variety of dopamine neurons membrane current mediated by NMDA agonist(the dose of NMDA were 0.1μM,1μM and 10μM) in the VTA.Results:1. The withdrawal symptoms were according with the scoring indications of the established heroin-addicted model of rats.2. Gave stimulation to the VTA and NAc respectively and induced LTP from NAc and VTA respectively on heroin-addicted group, the result showed that the PS amplitude of LTP was significantly lower than control group and abstinence group(P<0.05).3. The VTA's DA neurons membrane current mediated by NMDA receptor in heroin-addicted group was significantly lower than control group and abstinence group(P<0.05).4. The TH-immunoreactive of DA neurons in the VTA on heroin-addicted groups is up-regulated (P<0.05).Conclusion:1. The control group, heroin-addicted group and abstinence group rats could all induced LTP in the VTA, and the PS amplitude of LTP of heroin-addicted group is obviously lower than control group and abstinence group.2. The TH-immunoreactive of DA neurons in the VTA on heroin-addicted groups is enhanced.3. The VTA's DA neurons membrane current mediated by NMDA receptor was decreased in heroin-addicted group.