Histamine potentiates N-methyl-D-aspartate responses in acutely isolated hippocampal neurons

N-methyl-D-aspartate (NMDA)-evoked currents were recorded from acutely isolated rat hippocampal neurons, using the whole-cell patch-clamp technique and a rapid perfusion system. Histamine, at concentrations from 0.5 to 100 microM, reversibly enhanced NMDA currents by up to 50%. The effect cannot be ascribed to activation of the known histamine receptors (H1, H2, H3) but is occluded by spermine. These results suggest an interaction of histamine with the polyamine-binding site on the NMDA receptor complex. This modulatory action could allow the histaminergic system to determine time and loci of NMDA receptor-mediated events, such as memory formation according to behavioral state.