ABSTRACTAimsThis study aimed to investigate whether an aldehyde dehydrogenase (ALDH) activator (Alda-1®) reduces neuronal damage in a rat model of binge ethanol exposure.MethodsThirty-six adolescent male rats (130-150 g) were randomly assigned into three groups: sham, ethanol-only group (25% ethanol intragastrically thrice daily for four days, approximately 10 g/kg/day) and ethanol with Alda-1®group (10 mg/kg thrice daily for four days). The ALDH activity at baseline and 90 min after the last infusion in each group was measured. Brain damage was investigated using Luxol fast blue-Cresyl violet staining in the hippocampus, CA1 and CA2/3. The activation of astrocytes and microglia was examined using immunohistochemistry for antiglial fibrillary acidic protein (GFAP) and anti-ionized calcium-binding adapter molecule 1 (Iba-1).ResultsAfter a four-day binge, the ALDH activity level was doubled in the ethanol with Alda-1®group (mean: 7.87, SD: 0.67), whereas the levels in the sham group (mean: 4.07, SD: 0.53) and ethanol-only group (mean: 3.77, SD: 0.36) were slightly decreased. More significant neuronal shrinkage, fewer neurons, and loss of Nissl in the hippocampus were observed in the ethanol-only group compared to the ethanol with Alda-1®group. Astrocytosis and microgliosis of the hippocampus also showed increased activation in the ethanol only group compared with the ethanol with Alda-1®group.ConclusionAlda-1®administration reduces cytotoxic damage to the hippocampus in adolescent rats with binge ethanol exposure.