Oxytocin inhibits methamphetamine-associated learning and memory alterations by regulating DNA methylation at the Synaptophysin promoter.

摘要: Methamphetamine (METH) causes memory changes, but the underlying mechanisms are poorly understood. Epigenetic mechanisms, including DNA methylation, can potentially cause synaptic changes in brain. Oxytocin (OT) plays a central role learning and memory, little is known of impact OT on METH-associated changes. Here, we explored METH-induced epigenetic alterations that underlie spatial cognitive METH (2.0 mg/kg, i.p.) was administered to male C57BL/6 mice once every other day for 8 days. (2.5 μg, i.c.v.) or aCSF given prior METH. Spatial were assessed. In Hip PFC, structures proteins examined, levels methyltransferases (DNMTs) methyl CpG binding protein 2 (MECP2) determined, methylation status at Synaptophysin (Syn) promoter enhanced decreased synapse length, downregulated DNMT1, DNMT3A, DNMT3B, MECP2, induced hypomethylation Syn Hip. contrast, reduced increased thickness, upregulated hypermethylation PFC. pretreatment specifically ameliorated alterations, normalized structures, regulated DNMTs MECP2 reverse an important gene regulatory mechanism alterations. be used manipulate METH-related