Neuroscience Center, Biomedicum Helsinki, University of Helsinki, P.O. Box 63, Haartmaninkatu 8, FIN-00014 Helsinki, Finland.
Neuropharmacology. 2011 Jun;60(7-8):1193-9. doi: 10.1016/j.neuropharm.2010.10.027. Epub 2010 Oct 31.
Histamine H3 receptor (H3R) antagonists are currently being investigated for the possible therapeutic use in various cognitive deficits such as those in schizophrenia, attention deficit hyperactivity disorder and Alzheimer's disease. Our previous studies suggest a role for H3Rs in ethanol-related behaviors in rat and mice. Here we have examined the role of different H3R ligands on the effects of ethanol in conditioned place preference (CPP) paradigm, stimulation of locomotor activity and motor impairment in rotarod and balance beam in male DBA/2J mice. We found that H3R antagonists ciproxifan and JNJ-10181457 inhibited the ethanol-evoked CPP whereas H3R agonist immepip did not alter ethanol-induced place preference. Acute stimulatory response by ethanol was also modulated by H3R ligands. Ciproxifan increased ethanol activation when ethanol was given 1g/kg but not at 1.5g/kg dose. Immepip pretreatment diminished ethanol stimulation and increased motor-impairing effects of ethanol on the balance beam. In conclusion, these findings give further evidence of the involvement of H3R in the regulation of the effects of ethanol. The inhibition of ethanol reward by H3R antagonism implies that H3R might be a possible target to suppress compulsory ethanol seeking. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'.
组胺 H3 受体（H3R）拮抗剂目前正在研究用于治疗各种认知缺陷，如精神分裂症、注意缺陷多动障碍和阿尔茨海默病。我们之前的研究表明 H3R 在大鼠和小鼠的乙醇相关行为中起作用。在这里，我们研究了不同 H3R 配体在条件性位置偏爱（CPP）范式中对乙醇的影响、对运动活性的刺激作用以及在旋转棒和平衡梁上的运动障碍的作用，在雄性 DBA/2J 小鼠中。我们发现 H3R 拮抗剂西普昔芬和 JNJ-10181457 抑制了乙醇引起的 CPP，而 H3R 激动剂 immepip 没有改变乙醇引起的位置偏好。H3R 配体也调节了乙醇的急性刺激反应。西普昔芬增加了乙醇在 1g/kg 剂量时的激活作用，但在 1.5g/kg 剂量时没有增加。immepip 预处理减弱了乙醇的刺激作用，并增加了乙醇对平衡梁的运动障碍作用。总之，这些发现进一步证明了 H3R 参与调节乙醇的作用。H3R 拮抗作用抑制了乙醇的奖赏作用，这表明 H3R 可能是抑制强制性乙醇寻求的一个可能靶点。本文是特刊“神经药理学趋势：纪念 Erminio Costa”的一部分。
