Arrang Jean-Michel
INSERM, U573, Unité de Neurobiologie et Pharmacologie Moléculaire, Centre Paul Broca, 2 ter rue d'Alésia, 75014 Paris, France.
Int Rev Neurobiol. 2007;78:247-87. doi: 10.1016/S0074-7742(06)78009-6.
With the availability of an increased number of experimental tools, for example potent and brain-penetrating H1-, H2-, and H3-receptor ligands and mutant mice lacking the histamine synthesis enzyme or the histamine receptors, the functional roles of histaminergic neurons in the brain have been considerably clarified during the recent years, particularly their major role in the control of arousal, cognition, and energy balance. Various approaches tend to establish the implication of histaminergic neurons in schizophrenia. A strong hyperactivity of histamine neurons is induced in rodent brain by administration of methamphetamine or NMDA-receptor antagonists. Histamine neuron activity is modulated by typical and atypical neuroleptics. H3-receptor antagonists/inverse agonists display antipsychotic-like properties in animal models of the disease. Because of the limited predictability value of most animal models and the paucity of drugs affecting histaminergic transmission that were tried so far in human, the evidence remains therefore largely indirect, but supports a role of histamine neurons in schizophrenia.
随着越来越多实验工具的出现，例如强效且能穿透大脑的H1、H2和H3受体配体以及缺乏组胺合成酶或组胺受体的突变小鼠，近年来组胺能神经元在大脑中的功能作用已得到相当程度的阐明，尤其是它们在控制觉醒、认知和能量平衡方面的主要作用。各种方法倾向于证实组胺能神经元与精神分裂症有关。在啮齿动物大脑中，通过给予甲基苯丙胺或NMDA受体拮抗剂可诱导组胺神经元强烈的过度活跃。组胺神经元的活动受到典型和非典型抗精神病药物的调节。H3受体拮抗剂/反向激动剂在该疾病的动物模型中表现出类似抗精神病的特性。由于大多数动物模型的预测价值有限，且到目前为止在人体中尝试的影响组胺能传递的药物很少，因此证据在很大程度上仍然是间接的，但支持组胺神经元在精神分裂症中的作用。
