Induction of long-term posttetanic potentiation in rat hippocampal CA1 filed was followed by a decrease in the content of transcription factor p53 against the background of unchanged level of p53 mRNA, which implies activation of negative regulators of p53. Mdm2 is an important regulator of p53. We studied the effects of Mdm2 inhibitor nutlin-3 on p53 expression during generation of long-term posttetanic potentiation. Mdm2 inhibition completely prevented tetanization-induced decrease in the content of p53 protein; the level of p53 mRNA tended to increase in 30 min after tetanization. Thus, Mdm2 contributes to the maintenance of constant level of mRNA and plays a pivotal role in the decrease in the level of p53 protein during induction of long-term potentiation.