Sexually specific changes in ethanol-treated animals were frequently reported.It may logically be some sexual difference changes in the central nervous system (CNS).The present study aimed to examine the effects of chronic prenatal ethanol exposure (CPEE) on spatial cognition and synaptic plasticity in female rats.The female offspring were selected from the Wistar dams that were exposed to the ethanol throughout gestational period with 4 g/kg bodyweight.Morris water maze (MWM) tests were used to assess spatial cognition.Long-term potentiation (LTP) and depotentiation were measured in hippocampal CA3-CA1 pathway to investigate the cellular mechanisms of behavioral cognition.Results showed that escape latencies in learning and reversal learning stages were markedly prolonged under CPEE-treated condition, while LTP was dramatically enhanced and depotentiation observably reduced compared to that of normal rats.The data suggested that cognition flexibility of CPEE female was disrupted by synaptic plasticity imbalance.