Oleanolic acid protects ethanol-induced memory impairments

A moderate amount of ethanol (EtOH) intake can lower the incidence of various cardiovascular disease but can result in neuropsychiatric issues during adolescence. EtOH acts on GABA_A receptor, which can slow down neurotransmission and lead to changes in synaptic functions. These neurological changes due to EtOH can result in transient memory loss and may increase the risk of developing various neurological and psychiatric disorders such as dementia. Therefore, there is a need for strategies to overcome EtOH-induced brain dysfunctions. In this study, we investigated the effects of oleanolic acid (OA) on EtOH-induced memory impairment. OA blocked functional impairment of N-methyl-D-aspartate receptors (NMDAR), which are a key mechanism in EtOH-induced memory impairments. OA inhibited the removal of the major subunit of NMDAR, NR2a, from synapses induced by EtOH. Based on this, OA inhibited the impairment of object recognition memory caused by EtOH. Although OA failed to modulate the blood alcohol and acetaldehyde levels in EtOH-treated mice, OA blocked EtOH-induced increase in brain allopregnalone level with reducing 5α-reductase level. These results indicate that OA inhibits EtOH-induced memory impairment by regulating NMDAR function and passably modulates neurosteroid system.