γ-氨基丁酸B型受体（GABABR）调节机制被抑制与药物成瘾奖赏效应的建立和维持密切相关。我们前期研究发现：成瘾大鼠伏隔核（NAc）区域细胞膜GABABR水平减少与药物成瘾行为敏感化产生相关；抑制GABA能神经元Rab10表达能减少细胞膜GABABR水平。由此提出假说：Rab10介导GABA能神经元内GABABR上膜异常可能影响药物成瘾过程。本课题拟通过体内、体外实验，观察精神兴奋药物诱导GABA能神经元内GABABR上膜过程及其介导的离子通道改变情况，观察成瘾大鼠NAc区域慢性突触后抑制性信号传递（sIPSC）抑制和成瘾行为激活情况；同时通过激活/抑制GABA能神经元Rab10表达，研究在成瘾奖赏效应中Rab10介导GABABR上膜过程的分子机制。通过本课题执行期望明确在成瘾过程中NAc区域GABABR抑制性调节通路的分子机制，这对研发特异性的抑制成瘾药物将有十分重要的意义。

The regulation mechanism of the GABABR signaling on the mesolimbic system is closely related to the establishment and maintenance of drug addiction. Our previous studies have shown that the decrease of GABABR level in the cell membrane in the nucleus accumbens (NAc) region after the treatment of psychostimulous drug is related to the psychostimulous drug induced-behavioral sensitization; Inhibition of Rab10 expression of the GABA neuron reduces the level of GABABR in cell membrane. Thus the hypothesis has putted forward that the psychostimulous drug induced-abnormalities of GABABR membrane trafficking by the Rab10-vesicle in GABA neurons in the NAc region may affect the process of the drug addiction. In this study, we investigated the effects of psychostimulous drug in GABA neurons on the membrane trafficking of GABABR and the changes of GABABR mediated downstream ion channel in the NAc region; And to observe the inhibition of slow inhibitory postsynaptic current (sIPSC) and the increase of the locomotor activity in psychostimulous addicted animals; At the same time, we investigated the molecular mechanism of the GABABR membrane trafficking mediated by Rab10 in GABA neurons in psychostimulous drug induced-behavior sensitization after activating / inhibiting the expression of Rab10. This project is implemented that it is cleared that the inhibitory regulation mechanism of GABABR, which is closely related to drug addiction. It is of great significance for the development of specific inhibition of addictive drugs.