Manahan-Vaughan D, Reymann K G, Brown R E
Department of Neurophysiology, Institute for Neurobiology, Magdeburg, Germany.
Neuroscience. 1998 Jun;84(3):783-90. doi: 10.1016/s0306-4522(97)00540-x.
Drugs acting at the three known classes of histamine receptors were injected intracerebroventricularly into the rat. The effects of these drugs upon synaptic potentials recorded from the dentate gyrus of the freely-moving rat were determined. Population spikes and field excitatory postsynaptic potentials were recorded from the granule cell layer of the dentate gyrus following stimulation of the perforant path. Drugs, dissolved in 0.9% NaCl were applied into the lateral cerebral ventricle in a volume of 5 microl over a period of 6 min. The histamine H1 receptor antagonist mepyramine (0.4 or 0.8 microg) had no significant effect on population spikes or field excitatory postsynaptic potentials. In contrast the H2 receptor antagonist cimetidine (3.25, 6.5 or 13 microg) showed a biphasic effect. At the lower doses (3.25 or 6.5 microg) a small (15%) depression of the field excitatory postsynaptic potentials and population spikes was observed beginning about 1 h following the infusion. At the highest dose tested (13 microg) a marked increase of the population spike was observed beginning immediately following the infusion and lasting for 90 min. Application of the H3 receptor agonist R-alpha-methylhistamine (0.2 microg) depressed the field excitatory postsynaptic potentials (15% at 4 h post-injection) and even more strongly the population spike (50%). Surprisingly, at higher doses (0.4 and 0.8 microg) no effect was seen. The H3 receptor antagonist thioperamide (0.41 and 0.82 microg) did not cause an increase in synaptic potentials but rather at the highest dose a small depression occurred at later time points (2-4 h following the infusion). At the lower dose (0.41 microg) thioperamide blocked the effect of R-alpha-methylhistamine (0.2 microg). These results show that the histaminergic system modulates information flow through the dentate gyrus in a complex manner involving both histamine H2 and H1 receptors.
将作用于三类已知组胺受体的药物脑室内注射到大鼠体内。测定了这些药物对自由活动大鼠齿状回记录的突触电位的影响。在刺激穿通通路后，从齿状回颗粒细胞层记录群体峰电位和场兴奋性突触后电位。将溶解于0.9%氯化钠溶液中的药物以5微升的体积在6分钟内注入侧脑室。组胺H1受体拮抗剂美吡拉敏（0.4或0.8微克）对群体峰电位或场兴奋性突触后电位无显著影响。相比之下，H2受体拮抗剂西咪替丁（3.25、6.5或13微克）呈现双相效应。在较低剂量（3.25或6.5微克）时，输注后约1小时开始观察到场兴奋性突触后电位和群体峰电位有轻微（15%）降低。在测试的最高剂量（13微克）时，输注后立即观察到群体峰电位显著增加，并持续90分钟。应用H3受体激动剂R-α-甲基组胺（0.2微克）可降低场兴奋性突触后电位（注射后4小时降低15%），对群体峰电位的降低作用更强（50%）。令人惊讶的是，在较高剂量（0.4和0.8微克）时未观察到效应。H3受体拮抗剂硫代哌酰胺（0.41和0.82微克）未引起突触电位增加，而是在最高剂量时，在较晚时间点（输注后2 - 4小时）出现轻微降低。在较低剂量（0.41微克）时，硫代哌酰胺可阻断R-α-甲基组胺（0.2微克）的作用。这些结果表明，组胺能系统以涉及组胺H2和H1受体的复杂方式调节通过齿状回的信息流。
