Rizk Angela, Curley Justine, Robertson Jennifer, Raber Jacob
Department of Behavioural Neuroscience, Oregon Health and Science University, 3181 SW. Sam Jackson Park Road, Portland, OR 97239, USA.
Eur J Neurosci. 2004 Apr;19(7):1992-6. doi: 10.1111/j.1460-9568.2004.03251.x.
Histamine H(3) receptors (H3Rs) were first characterized as autoreceptors modulating histamine release and synthesis via negative feedback. Acute H3R stimulation or blockade with selective agonists and antagonists suggests a role for H3R in anxiety and cognition. However, little is known about the long-term effects of H3R blockade on brain function. In the current study, mice lacking H3 receptors (H3R(-/-)) were used to investigate the role of H3R-mediated signalling in anxiety and cognition. H3R(-/-) mice showed enhanced spatial learning and memory in the Barnes maze. In addition, H3R(-/-) mice showed reduced measures of anxiety in the elevated plus and zero mazes involving exploratory behaviour and avoidable anxiety-provoking stimuli, but enhanced acoustic startle responses involving unavoidable anxiety-provoking stimuli. These behavioural alterations were associated with higher arginine vasopressin levels in the central and basolateral nuclei of the amygdala. These findings support a role for H3Rs in mediating histamine effects on spatial learning and memory and measures of anxiety.
组胺H(3)受体（H3Rs）最初被鉴定为通过负反馈调节组胺释放和合成的自身受体。急性H3R刺激或用选择性激动剂和拮抗剂阻断表明H3R在焦虑和认知中起作用。然而，关于H3R阻断对脑功能的长期影响知之甚少。在当前研究中，使用缺乏H3受体（H3R(-/-)）的小鼠来研究H3R介导的信号传导在焦虑和认知中的作用。H3R(-/-)小鼠在巴恩斯迷宫中表现出增强的空间学习和记忆能力。此外，H3R(-/-)小鼠在涉及探索行为和可避免的焦虑诱发刺激的高架十字迷宫和零迷宫中表现出焦虑测量值降低，但在涉及不可避免的焦虑诱发刺激的听觉惊吓反应中增强。这些行为改变与杏仁核中央和基底外侧核中较高的精氨酸加压素水平有关。这些发现支持H3Rs在介导组胺对空间学习和记忆以及焦虑测量的影响中起作用。
