ObjectiveImmediate postictal potentiation (PIP), a unique phenomenon observed in immature animals, may contribute to the enhanced sensitivity of young animals to seizures and epilepsy. PIP deserves more experimental attention because understanding its mechanisms could provide valuable insights into treating these conditions.MethodsUsing the technique of cortical afterdischarges (ADs), we analyzed the effect of glutamate receptor antagonists on PIP in 12-day-old rats. A conditioning AD was recorded, followed 1 min later by a test AD. Then, an antagonist was administered, and 10 min later, another pair of ADs was elicited.ResultsThe most pronounced effect was observed with ifenprodil, a selective antagonist of NMDA receptors that contain the GluN2B subunit, which is the dominant form in immature animals. This antagonist not only suppressed the immediate PIP but also converted the condition to an adult-like postictal depression. Post-drug, the test AD was significantly shorter than the conditioning AD. Less pronounced effects were found with non-selective NMDA antagonists, antagonists that preferntially target NMDA receptors containing the GluN2A subunit (which is the dominant form in adult animals), or metabotropic glutamate receptor antagonists. In contrast, AMPA antagonists had their major effects on delayed PIP. This was particularly true for IEM 1460, a selective antagonist of AMPA receptors that lack a functional GluR2 subunit, which is again a form predominant in immature animals.ConclusionPIP appears to be a function of the unique structure of glutamate receptors in the immature nervous system, particularly NMDA receptors.HighlightsPostictal potentiation (PIP) rather than depression is observed in immature rats.Two types of PIP are identified—immediate (up to 5 min) and delayed.Immediate PIP is due to NMDA receptors containing the NR2B subunit.Delayed PIP is a more complicated phenomenon. Among systems participating in delayed PIP, AMPA receptors play a role.