Adolescents diagnosed with an alcohol use disorder show neurodegeneration in the hippocampus, a region important for learning, memory, and mood regulation. This study examines a potential mechanism by which excessive alcohol intake, characteristic of an alcohol use disorder, produces neurodegeneration. As hippocampal neural stem cells underlie ongoing neurogenesis, a phenomenon that contributes to hippocampal structure and function, we investigated aspects of cell death and cell birth in an adolescent rat model of an alcohol use disorder. Immunohistochemistry of various markers along with Bromo-deoxy-Uridine (BrdU) injections were used to examine different aspects of neurogenesis. After 4 days of binge alcohol exposure, neurogenesis was decreased by 33% and 28% at 0 and 2 days after the last dose according to doublecortin expression. To determine whether this decrease in neurogenesis was due to effects on neural stem cell proliferation, quantification of BrdU-labeled cells revealed a 21% decrease in the dentate gyrus of alcohol-exposed brains. Cell survival and phenotype of BrdU-labeled cells were assessed 28 days after alcohol exposure and revealed a significant, 50% decrease in the number of surviving cells in the alcohol-exposed group. Reduced survival was supported by significant increases in the number of pyknotic-, FluoroJade B positive-, and TUNEL-positive cells. However, so few cells were TUNEL-positive that cell death is likely necrotic in this model. Although alcohol decreased the number of newborn cells, it did not affect the percentage of cells that matured into neurons (differentiation). Thus, our data support that in a model of an adolescent alcohol use disorder, neurogenesis is impaired by two mechanisms: alcohol-inhibition of neural stem cell proliferation and alcohol effects on new cell survival. Remarkably, alcohol inhibition of neurogenesis may outweigh the few dying cells per section, which implies that alcohol inhibition of neurogenesis contributes to hippocampal neurodegeneration in alcohol use disorders. Keywordsethanol; alcoholism; neural stem cell; progenitor; cell deathThe likelihood of developing an alcohol use disorder (AUD) triples in adolescents who begin drinking younger than 14 versus after age 18 (SAMHSA, Administration, 2008). Over 70 percent of teens have tried alcohol by the 12 th grade with "heavy drinking" (five or more drinks in one sitting in the last two weeks) or "having been drunk" reported in 25 to 30 percent of 17-18 year olds respectively (Johnston et al., 2007). Indeed, over five percent of 12-17 year olds meet the diagnostic criteria for an AUD (Harford et al., 2005). Adolescents drink quantities of alcohol similar to adults due to their pattern of intake (Deas et al., 2000 Approximately 60% of high school students who currently drink alcohol are binge drinkers (5 or more drinks/occasion; Zeigler et al., 2005). A binge drinking pattern is one of the few factors which predicts brain damage from alcohol (Hunt, 1993), which has led several groups to propose th...