Two aspects of the excitatory influence of histamine on hippocampal neurons in guinea pigs.

The effect of histamine (Hi) on CA3 pyramidal cells in guinea pig hippocampal slices was studied by means of intracellular recordings in association with electrical stimulation to the mossy fibers of granular cells. The amplitude of EPSPs and spikes was augmented significantly by Hi at concentrations of 10(-7) to 10(-6) M. The stimulatory effect of Hi was mimicked by the H2-agonist dimaprit (10(-6) M), but not by the H1-agonist 2-thiazolylethylamine (10(-5) M). An increase in EPSPs or spikes was provoked during perfusion of dibutyryl cAMP at concentrations higher than 10(-6) M. Intracellular application of cAMP to the pyramidal cells augmented the amplitude of EPSPs. The amplitude of IPSPs provoked by GABA was reduced by simultaneous perfusion of Hi at concentrations of 10(-7) M to 10(-6) M. The Hi-induced reduction was not blocked by either pyrilamine, cimetidine or thioperamide. It became clear that Hi exerts an excitatory influence on the hippocampal neurons, not only by stimulating the excitatory system via an H2-receptor coupled with Hi-sensitive adenylate cyclase, but also by depressing the inhibitory system, which may be mediated by GABA.