Foods contaminated with melamine potentially cause risk to human health. However, the neurotoxicity of melamine has not been adequately assessed. Here, we aimed to examine the effects of acute low-dose exposure to melamine on hippocampal synaptic plasticity and behaviors in rats. We found that bath application of 50-500 mu g/ml melamine decreased basal synaptic transmission in the Schaffer collateral-CA1 pathway of hippocampal slices from postnatal days (P) 10-14 rats in a concentration-dependent manner; furthermore, this decrease in transmission was related to the reduction of presynaptic function as indicated by the increased paired-pulse facilitation ratio. Rats at 2-3 months old were less vulnerable to the effects of 500 mu g/ml melamine on basal synaptic transmission when compared with P10-14 and P21-28 rats. Melamine (50 mu g/ml) significantly impaired long-term potentiation (LTP), without affecting long-term depression (LTD), in both P10-14 and 2-3 month-old rats. Oral treatment with melamine (5 and 25 mg/kg) 1 h before behavioral tests significantly decreased the immobility time of the forced swim test in 2-3 month-old rats and had no effect on locomotor activity in the open field test in both P21-28 and 2-3 month-old rats. Our findings reveal some of the aspects of neurotoxicity induced by acute low-dose of melamine in hippocampal synaptic plasticity and behavior. (c) 2012 Elsevier Ireland Ltd. All rights reserved.