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

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. *Corresponding author: Min Hu, Department of Ophthalmology, The Second People’s Hospital of Yunnan Province, Kunming City, PR China, Tel: 08615996914018; E-mail: [email protected] Received February 16, 2016; Accepted March 31, 2016; Published April 07, 2016 Citation: Niu H, Zhang Q, Guo L, Hu M (2016) Blockade of Lactate Transport in the Insular Cortex Impairs Reconsolidation, but not Retrieval, of Morphine-associated Memory and Prevents Subsequent Reinstatement. J Alzheimers Dis Parkinsonism 6: 227. doi: 10.4172/2161-0460.1000227 Copyright: © 2016 Niu H, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. During abstinence, drug-related cues induce drug-seeking behaviors by the activation of reward memory. The insular cortex is a key cortical region for activation, which is regulated by the interoception procedure for reward memory [13]. Viscerosensory and nociceptive nonspecific thalamic inputs were transmitted into the insular cortex, which stores emotional and affective state information in the parahippocampal-hippocampal system [14]. Reward effects of morphine and environmental cues were integrated to become reward memories. Therefore, disturbing the insular cortex may contribute to the reconsolidation of reward memory. Previous studies have indicated that metabolic coupling between astrocytes and neurons is considered a key mechanism in response to neuronal activity [15]. Further studies have shown that interference with lactate transfer from astrocytes to neurons could affect this memory procedure. The astrocyte network could be interconnected through gap junctions to form many synapses, thereby permitting a continuous supply of energy substrates [16]. Astrocytic storage of Citation: Niu H, Zhang Q, Guo L, Hu M (2016) Blockade of Lactate Transport in the Insular Cortex Impairs Reconsolidation, but not Retrieval, of Morphine-associated Memory and Prevents Subsequent Reinstatement. J Alzheimers Dis Parkinsonism 6: 227. doi: 10.4172/21610460.1000227