| 1 The effects of histamine on MK-801-induced spatial memorydeficits in SD ratsRecently, the differentiation of functions along the longitudinal axis of the hippocampus (dorsal-ventral in the rat and posterior-anterior in humans) has attracted interest. Anatomically, the hippocampus includes CA1, CA2, CA3, and dentate gyrus subfields, with the pattern of efferent and afferent connectivity changing between the dorsal and ventral hippocampus. Identification of distinct functional roles for the dorsal and ventral hippocampus may help to resolve differences among the various theoretical accounts of hippocampal involvement in learning behavior. Chemical lesion study on the hippocampus demonstrated that the VH is less related to spatial memory modulation, but some studies demonstrated that the VH may be also involved in acquisition of spatial memory. And histamine is a neurotransmitter which plays an important role in learning and memory. Recently, the interactions between histamine and NMDA receptor have attracted considerable attentions. It was been reported that histamine potentiated the NMDA-mediated synaptic plasticity in hippocampal slice. However, there is little research about it in memory process in vivo. So our Aim: To investigate the role of histamine in memory deficits induced by MK-801 infusion into the ventral hippocampus in rats. Methods: An 8-arm radial maze (4 arms baited) was used to assess spatial memory. Results: Bilateral ventral intrahippocampal (ih) infusion of MK-801 (0.3 μg/site), an N-methyl-D-aspartate (NMDA) antagonist, impaired the retrieval process in bothworking memory and reference memory. In the ventral hippocampus, intrahippocampal injection of histamine (25 or 50 ng/site) or intraperitoneal (ip) injection of histidine (25,50 or 100 mg/kg) markedly ameliorated the spatial memory deficits induced by MK-801. Both the histamine Hi antagonist pyrilamine (0.5 or 1.0 |j.g/site, ih) and the H2 antagonist cimetidine (2.5 |ag/site,#ih) abolished the ameliorating effect of histidine (100 mg/kg, ip) on reference memory deficits, but not that on working memory deficits induced by MK-801. Conclusion: The results indicate that histamine in the ventral hippocampus can ameliorate MK-801-induced spatial memory deficits. In the ventral hippocampus, the effect of histamine on reference memory is mediated by postsynaptic histamine Hi and H2 receptors.2 Ameliorative effcets of histamine on spatial memory deficits induced by scopolamine infusion into bilateral dorsal or ventral hippocampus as evaluated by radial maze taskChemical lesion study on the hippocampus demonstrated that the VH is less related to spatial memory modulation, but some studies demonstrated that the VH may be also involved in acquisition of spatial memory, and in our recent study, we have found a blockade of NMDA receptors in the VH impairs the retrieval of spatial working and reference memory, which suggests that the VH may be involved in the spatial memory process in rats. Recently, the interaction between histaminergic and cholinergic systems in learning and memory is of considerable interest. So our Aim: To examine the roles of hippocampal histaminergic system in the regulation of spatial memory deficit induced by scopolamine infused into the DH or VH. Methods: An8-arm radial maze (4 arms baited) was used to assess spatial memory. Results: Both bilateral dorsal and ventral hippocampal injections (ih) of scopolamine impaired spatial memory in retrieval memory process. In the DH, ih injection of histamine (50, 100 ng/site) and interaperitoneal injection (ip) of histidine (50,100 mg/kg) markedly improved working memory deficits induced by scopolamine, and histamine (50 ng/site, ih) and histidine (100 mg/site, ip) improved reference memory deficits. Histamine Hi antagonist pyrilamine (1 (ag/site, ih) significantly abolished the ameliorating effect of histidine (100 mg/kg, ip) on working memory deficits, pyrilamine (0.5, 1 (J.g/site, ih) and H2 antagonist cimetidine (0.5 |ag/site, ih) significantly abolished the ameliorating effect of histidine on reference memory. In the VH, histamine (25, 50 ng/site, ih) and histidine (50, 100 mg/kg, ip) markedly improved working memory deficits induced by scopolamine, but not improved reference memory. Both pyrilamine (0.2, 0.5, 1 jag/site, ih) and cimetidine (0.1, 0.5 jag/site, ih) reversed the effect of histidine. Conclusion: The results indicate that histamine expresses different functions in the DH and VH. Histamine in the DH ameliorates scopolamine-induced spatial working and reference memory deficits and the ameliorating effect of histamine on working memory is mediated by postsynaptic Hi receptors and the effect on reference memory is mediated by postsynaptic Hi and H2 receptors;histamine in the VH only ameliorates scopolamine-induced working memory deficits and the effect of histamine is mediated by Hi receptors and H2 receptors. |
PDF Full Text Request