阿尔茨海默病和帕金森病杂志

抽象的

Blockade of Lactate Transport in the Insular Cortex Impairs Reconsolidation, but not Retrieval, of Morphine-associated Memo ry and Prevents Subsequent Reinstatement

Yan Nie, He Ren, Jia-Rui Gu, Chong-Ran Sun, Yang Hui, Yong-Bin Jing and En-You Li

Drug-associated memories are critical for addictive behaviors, as these memories can trigger drug seeking and relapse by contextual cues. The transfer of lactate from astrocytes to neurons plays an important role in reward memory. Recently, studies have indicated that the insular cortex has a vital role in addictive procedure, which can be induced by contextual cues using both rat and human memory models. However, the neural locus in which the role of astrocyte–neuron lactate transport in long-term conditioning is required for reward memories is unclear. In investigating the involvement of insular astrocyte–neuron lactate transport in the processing of reward memory, using the conditioned place preference (CPP), we show that the local blockage of astrocyte–neuron lactate transport via the infusion of an inhibitor of glycogen phosphorylase (DAB) into the insular cortex impairs CPP expression of reconsolidation, but not extinction. Co-administering L-lactate and DAB confirmed that lactate could restore DABinduced memory deficit. The expression of c-fos in the insula cortex, the product of an immediate early gene, is also inhibited following memory reactivation. We found that the administration of DAB in the insula prior to reactivating the memory could inhibit the reconsolidation of reward memory, which could be reversed by the co-administration of DAB and L-lactate, and decrease the number of c-fos-positive cells. However, these treatments have no contribution to the extinction procedure, thereby indicating that the inhibitory contribution is reactivation dependent. Our results demonstrate that insular astrocyte–neuron lactate transport has a role in the processing of drug memory and that the blockage of insular astrocyte–neuron lactate transport could inhibit the reconsolidation of reward memory. This offers a novel therapeutic target to reduce the long-lasting conditioned responses to drug abuse.