Dopamine is an important neurotransmitter in the brain, which participates in many activities of human beings and mammals under physiological and pathological conditions, especially plays a key role in exercise regulation, learning and memory and drug addiction. Neurons that produce neurotransmitter dopamine (dopaminergic neurons) adopt a management mode similar to "returning to satellites", release dopamine according to the needs of brain activities, and at the same time use dopamine transporters as "recovery pumps" to recover the released dopamine in a timely and appropriate amount, which not only achieves the purpose of adjusting the extracellular dopamine concentration to meet the needs of physiological activities, but also enables dopamine to be reused, saving energy and increasing efficiency. Once the dopamine "recovery pump" system fails, many central nervous system diseases will occur, such as drug addiction. So, how is the "recovery pump" of dopamine accurately adjusted? At present, the academic understanding of this process is still very limited.

Under the guidance of a team composed of researcher Zhou Jiawei, assistant researcher Zhu Shuyong, doctoral students Zhao Chengjiang and Wu Yingying from the Institute of Neuroscience, Shanghai Institute of Life Sciences, Chinese Academy of Sciences, after years of painstaking research, it was found that a regulator of small G protein, Vav2, can significantly change the transport efficiency of dopamine "recovery pump" system by regulating the distribution of dopamine transporters in plasma membrane. If the Vav2 gene is knocked out, the function of the "recovery pump" will be abnormally improved, and the dopamine content in the nucleus accumbens of the brain will be significantly increased. In order to find the "switch" to control dopamine "recovery pump", the researchers used molecular biology experiments to screen the receptor Ret of glial cell-derived neurotrophic factor GDNF.

Their research results show that GDNF and Ret can be used as "switches" to switch and adjust dopamine "recovery pump". When this set of "switches" fails (such as Ret gene knockout), animals behave like Vav2 gene knockout mice. In the past, it was generally believed that GDNF and its receptor Ret were mainly responsible for the survival of dopaminergic neurons. Therefore, their findings have expanded people's traditional understanding of the role of neurotrophic factor GDNF.

It is worth mentioning that the above-mentioned regulation mechanism of dopamine "recovery pump" has the specificity of brain region, and this "switch" mainly plays a role in the nucleus accumbens, a brain region related to reward and drug addiction. For a long time, people don't know much about whether there are differences in the regulation mechanism of dopamine "recovery pump" between the main dopaminergic systems in the brain. Therefore, this achievement of Zhou Jiawei's research group reveals the significant differences between nucleus accumbens and other major dopaminergic systems at the molecular level, which will provide an important theoretical basis for understanding and regulating the formation process of drug addiction. Indeed, in this study, they found that the disorder of dopamine "recovery pump" mechanism caused by Vav2 gene deletion can effectively inhibit the formation of drug addiction caused by cocaine, indicating that as a brand-new signal transduction pathway, GDNF/Ret/Vav2 signal transduction pathway plays a potentially important role in the treatment of cocaine addiction.