Blockage of histamine H1 receptor attenuates social isolation-induced disruption of prepulse inhibition: a study in H1 receptor gene knockout mice
Blockage of histamine H1 receptor attenuates social isolation-induced disruption of prepulse inhibition: a study in H1 receptor gene knockout mice
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DOI：
10.1007/s00213-005-0203-4
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发表时间：
2005-10
影响因子：
3.4
通讯作者：
H. Dai;T. Okuda;E. Sakurai;Atsuo Kuramasu;Motohisa Kato;F. Jia;A. Jing Xu;K. Iinuma;Ikuro Sato;K. Yanai
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文献类型：
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作者：
H. Dai;T. Okuda;E. Sakurai;Atsuo Kuramasu;Motohisa Kato;F. Jia;A. Jing Xu;K. Iinuma;Ikuro Sato;K. Yanai
组胺能神经传递与应激相关的精神疾病的病理生理学有关。尽管一些非典型抗精神病药是有效的H1受体拮抗剂，但非典型抗精神病药与H1受体之间相互作用的临床意义仍然未知。我们研究了H1受体阻断对H1受体基因敲除（H1 KO）小鼠及其野生型（WT）小鼠社交隔离诱导的行为变化的影响。断奶后1周社会隔离饲养（产后21天）。4周的隔离期后，小鼠的行为变化进行了评估，使用行为tests.ResultsLocomotor活动在家庭笼隔离饲养的WT小鼠比社会饲养的WT小鼠显着降低。然而，在社会和隔离饲养的H1KO小鼠之间没有观察到自发活动的变化。社会隔离显着损害WT小鼠的惊吓反应的前脉冲抑制（PPI），但在H1KO小鼠。此外，社会隔离显著损害WT小鼠的空间学习和记忆，但在H1KO小鼠中没有。此外，用甲基苯丙胺（METH）处理的H1KO小鼠在隔离诱导的PPI破坏中没有表现出增强。一项神经化学研究显示，与社会饲养的WT小鼠相比，隔离饲养的WT小鼠大脑皮层中的多巴胺（DA）水平显著降低，DA周转率略有增加。相反，隔离饲养的H1KO小鼠表现出显着较高的DA含量相比，社会饲养的H1KO mice.Conclusion：我们的研究结果表明，H1受体介导的神经传递的阻断减弱社会隔离引起的行为变化和非典型抗精神病药物的治疗效果介导，至少部分，通过与H1受体在大脑中的相互作用。
RationaleHistaminergic neurotransmission has been implicated in the pathophysiology of stress-related psychiatric diseases. Although several atypical antipsychotics are potent H1 anagonists, the clinical significance of interaction between atypical antipsychotics and H1 receptors is still unknown.ObjectiveIn this study, we investigated the effects of H1 receptors blockage on social isolation-induced behavioral changes in H1 receptor gene knockout (H1KO) mice and their wild-type (WT) mice.MethodsBoth H1KO and their WT mice were subjected to 4-week social isolation rearing after weaning (21 postnatal days). After the 4-week isolation period, mice behavioral changes were evaluated using behavioral tests.ResultsLocomotor activity in home cages was significantly lower in isolation-reared WT mice than in socially reared WT mice. However, no change in locomotor activity was observed between socially and isolation-reared H1KO mice. Social isolation significantly impaired prepulse inhibition (PPI) of startle response in WT mice but not in H1KO mice. In addition, social isolation significantly impaired spatial learning and memory in WT mice but not in H1KO mice. Furthermore, H1KO mice treated with methamphetamine (METH) showed no enhancement in isolation-induced disruption of PPI. A neurochemical study revealed that isolation-reared WT mice had significantly lower dopamine (DA) levels and slightly increased DA turnover in the cortex than socially reared WT mice. Conversely, isolation-reared H1KO mice showed significantly higher DA contents as compared with socially reared H1KO mice.Conclusion:The results of our study indicate that blockage of H1 receptor-mediated neurotransmission attenuates social isolation-induced behavioral changes and that the therapeutic effects of atypical antipsychotics are mediated, at least in part, by interaction with H1 receptors in the brain.