Astrocyte-derived lactate/NADH alters methamphetamine-induced memory consolidation and retrieval by regulating neuronal synaptic plasticity in the dorsal hippocampus

AbstractDrug memory is associated with drug-taking experience and environmental cues, which mainly contribute to addiction. Recent studies report that glycogenolysis-derived lactate from astrocyte transport to neurons is necessary for long-term potentiation and memory formation instead of its function as an energy substrate. However, the role of astrocyte-neuron lactate transfer in neuronal plasticity and methamphetamine (METH)-induced addiction memory consolidation and retrieval, especially the underlying mechanisms, are not clear. C57BL/6  J mice trained for METH-induced conditioned place preference (CPP) were stereotaxically injected with the glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) into the dorsal hippocampus (dHPC) 15 min before training. The CPP score was recorded, and neuronal synaptic plasti city was detected with Golgi staining. The neuronal Ca2+ levels were examined using AAV-GCaMP6 injection. Moreover, monocarboxylate transporters (MCT1, MCT2, MCT4) were inhibited with oligodeoxynucleotides in the dHPC to further prove the METH appetitive memory changes. The data showed that inhibiting lactate transport by microinjection with DAB or monocarboxylate transporter oligodeoxynucleotides in the dHPC completely destroyed METH-induced CPP, reduced Npas4 and other plasticity-associated gene expression and decreased neuronal Ca2+ levels and neuronal arborization and spine density, all of which were fully rescued by L-lactate coadministrat...
Source: Anatomy and Embryology - Category: Anatomy Source Type: research