Histamine modulation of glutamate release from hippocampal synaptosomes

Abstract Histamine is widely believed to act as a neuromodulator in the central nervous system. Histaminergic fibers arriving at the hippocampus could be involved in the modulation of glutamatergic neurotransmission. Therefore, we have investigated the effect of histamine on [ 3 H]glutamate release from hippocampal synaptosomes by using a superfusion system. Calcium-dependent [ 3 H]glutamate release was stimulated by KCl or 4-aminopyridine. When submaximal concentrations of the depolarizing agents were used (15 mM KCl or 50 μM 4-aminopyridine), histamine, acting via histamine H 1 and H 2 receptors, produced a concentration-dependent increase in the evoked release of glutamate. Maximal effect was obtained with 500 μM histamine. Histamine (up to 1 mM) did not modify basal release. These data suggest that histaminergic afferents may modulate activity-dependent glutamatergic presynaptic terminals in the hippocampus.