Flik Gunnar, Folgering Joost H A, Cremers Thomas I H F, Westerink Ben H C, Dremencov Eliyahu
Brains On-Line BV, De Mudden 16, 9747 AW, Groningen, The Netherlands.
J Mol Neurosci. 2015 Jun;56(2):320-8. doi: 10.1007/s12031-015-0536-3. Epub 2015 Mar 29.
Brain monoamines (serotonin, norepinephrine, dopamine, and histamine) play an important role in emotions, cognition, and pathophysiology and treatment of mental disorders. The interactions between serotonin, norepinephrine, and dopamine were studied in numerous works; however, histamine system received less attention. The aim of this study was to investigate the interactions between histamine and other monoamines, using in vivo microdialysis and electrophysiology. It was found that the inverse agonist of histamine-3 receptors, thioperamide, increased the firing activity of dopamine neurons in the ventral tegmental area. Selective agonist of histamine-3 receptors, immepip, reversed thiperamide-induced stimulation of firing activity of dopamine neurons. The firing rates of serotonin and norpeinephrine neurons were not attenuated by immepip or thioperamide. Thioperamide robustly and significantly increased extracellular concentrations of serotonin, norepinephrine, and dopamine in the rat prefrontal cortex and slightly increased norepinephrine and dopamine levels in the tuberomammillary nucleus of the hypothalamus. It can be concluded that histamine stimulates serotonin, norepinephrine, and dopamine transmission in the brain. Modulation of firing of dopamine neurons is a key element in functional interactions between histamine and other monoamines. Antagonists of histamine-3 receptors, because of their potential ability to stimulate monoamine neurotransmission, might be beneficial in the treatment of mental disorders.
脑单胺类物质（血清素、去甲肾上腺素、多巴胺和组胺）在情绪、认知以及精神障碍的病理生理学和治疗中发挥着重要作用。血清素、去甲肾上腺素和多巴胺之间的相互作用已在众多研究中得到探讨；然而，组胺系统受到的关注较少。本研究的目的是利用体内微透析和电生理学方法，研究组胺与其他单胺类物质之间的相互作用。研究发现，组胺-3受体反向激动剂硫代哌啶可增加腹侧被盖区多巴胺神经元的放电活动。组胺-3受体选择性激动剂依美哌啶可逆转硫代哌啶诱导的多巴胺神经元放电活动刺激。依美哌啶或硫代哌啶并未减弱血清素和去甲肾上腺素能神经元的放电频率。硫代哌啶显著且强力地增加了大鼠前额叶皮质中血清素、去甲肾上腺素和多巴胺的细胞外浓度，并轻微增加了下丘脑结节乳头核中去甲肾上腺素和多巴胺的水平。可以得出结论，组胺可刺激大脑中的血清素、去甲肾上腺素和多巴胺传递。多巴胺神经元放电的调节是组胺与其他单胺类物质之间功能相互作用的关键因素。组胺-3受体拮抗剂因其潜在的刺激单胺类神经传递的能力，可能对精神障碍的治疗有益。
