Drug addiction is a major global public health and social problem, and according to the 2023 World Drug Report, there are 29.6 billion people have used drugs at least once, and 39.5 million of them have a substance use disorder. Drug addiction is a chronic brain disease, and its core and difficult to solve problem is the long-term psychological craving after withdrawal and the resulting relapse behavior. After drug withdrawal, the psychological craving induced by clues will gradually increase with the increase of time, this phenomenon is called the latent psychological craving of drug addiction, and how to intervene and eliminate the latent psychological craving is the key and difficult point of addiction. **The amygdala is involved in the occurrence and development of latent psychological cravings, but its specific molecular mechanism has not been elucidated. Lactate is an important energy of the central nervous system**, and lactate and lactate transport between glial cells and neurons are involved in regulating the function of the central nervous system, mediating neuroplasticity changes, long-term memory formation and rewarding memory reconsolidation processes, but it is unclear whether lactate and lactate transport are involved in the latent psychological craving induced by drug-related cues. Recently, the China Institute of Drug Dependence, Peking UniversityShi JieThe team of professors is inscience advancesThe journal ** published a publication entitled:disrupting astrocyte-neuron lactate transport prevents cocaine seeking after prolonged withdrawalResearch**,The study found that lactate and lactate transport between astrocytes and neurons play an important role in the process of latent psychological craving for cocaine, and inhibiting lactate production and lactate transport in the amygdala can reduce the psychological craving induced by cocaine-related cues during withdrawal
The researchers first administered ** amygdala glycogen phosphorylation inhibitor (1,4dideoxy-1,4iminodarabinitol (DAB) on the 30th day of withdrawal to intervene in lactate production, and the results of magnetic resonance spectroscopy showed that the concentration of lactate in the amygdala increased with the prolongation of withdrawal time, and DAB could reduce the increase in lactate level caused by drug withdrawal, and significantly reduce the latent psychological craving of rats. Using patch-clamp techniques, DAB was found to be able to reduce the excitatory input of neurons in the amygdala. Exogenous lactate supplementation reversed the effects of DAB and restored the reduced latent cravings and the expression of some synaptic plasticity-related proteins. Further exploration of the lactate transport process showed that compared with the first day of withdrawal, the monocarboxylate transporter in the amygdala, The expression levels of MCT2 and MCT4 were significantly increased on the 30th day of withdrawal, while the use of oligodeoxynucleotides or short hairpin RNA viruses with specific promoters to specifically reduce the levels of MCT2 or MCT4 could effectively reduce latent psychological craving, and weaken neuronal excitatory synaptic transmission function and the expression of some synaptic plasticity-related proteins. Exogenous lactate supplementation can only restore the decrease in latent psychological craving caused by the reduction of MCT4, but does not affect the changes caused by the reduction of MCT2. This study clarified the important role of glial-neuronal energy metabolism in the amygdala in the process of latent psychological craving after drug withdrawal, and the blocking of lactate production or astrocyte-neuronal lactate transport significantly reduced the psychological craving induced by drug-related cues during withdrawal, providing a new direction for drug addiction and prevention of relapse. 
Dr. Minjun Chen, Prof. Yan Zhang, and Dr. Jie Liang from the Chinese Institute of Drug Dependence, Peking University are the co-first authors of this paper, and Prof. Shi Jie, Academician Lu Lin, and Associate Prof. Ying Han are the co-corresponding authors of this paper. Original link: