Histamine modulation of glutamate release from hippocampal synaptosomes

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 [3H]glutamate release from hippocampal synaptosomes by using a superfusion system. Calcium-dependent [3H]glutamate release was stimulated by KCI or 4-aminopyridine. When submaximal concentrations of the depolarizing agents were used (15 mM KCI or 50 microM 4-aminopyridine), histamine, acting via histamine H1 and H2 receptors, produced a concentration-dependent increase in the evoked release of glutamate. Maximal effect was obtained with 500 microM 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.