Yuzurihara M, Ikarashi Y, Ishige A, Sasaki H, Kuribara H, Maruyama Y
Kampo and Pharmacognosy Laboratories, Tsumura, 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan.
Pharmacol Biochem Behav. 2000 Sep;67(1):145-50. doi: 10.1016/s0091-3057(00)00320-8.
Experimental anxiety in mice was evaluated using a light/dark test at 60 min after injection of various histaminergics. Thioperamide, a histamine H(3) receptor inhibitor (5-20 mg/kg, intraperitoneal [IP]), Compound 48/80, a mast cell degranulator (0.1-10 microg/2 microl, intracerebroventricularly [ICV]), mepyramine, a histamine H(1) receptor antagonist (0.1-10 microg/2 microl, ICV) or cimetidine, a histamine H(2) receptor antagonist (0.1-10 microg/2 microl, ICV) alone did not affect the locomotive activity, the time spent in the light zone, and number of shuttle crossings in the light/dark test. However, the time spent in the light zone and the number of shuttle crossings significantly decreased only when cimetidine (0.1-10 microg/2 microl, ICV) was co-treated with either thioperamide (10 mg/10 ml/kg, IP) or Compound 48/80 (1.0 microg/2 microl, ICV). The decrease in these behavioral parameters suggests induced experimental anxiety in mice. The experimental anxiety was antagonized by mepyramine (10 microg/2 microl, ICV). These results suggest that not only neuronal histamine release induced by thioperamide but also non-neuronal (mast cells) histamine release induced by Compound 48/80 play an important role in inducing experimental anxiety via post-synaptic H(1) and H(2) receptors. In addition, it is likely that the anxiety may be mediated by the stimulation of H(1) receptors, while H(2) receptors may inhibit the anxiety produced by the activation of H(1) receptors.
在注射各种组胺能药物60分钟后，通过明暗箱试验评估小鼠的实验性焦虑。组胺H(3)受体抑制剂硫代酰胺（5 - 20毫克/千克，腹腔注射[IP]）、肥大细胞脱颗粒剂化合物48/80（0.1 - 10微克/2微升，脑室内注射[ICV]）、组胺H(1)受体拮抗剂美吡拉敏（0.1 - 10微克/2微升，ICV）或组胺H(2)受体拮抗剂西咪替丁（0.1 - 10微克/2微升，ICV）单独使用时，并不影响明暗箱试验中的运动活性、在亮区停留的时间以及穿梭次数。然而，仅当西咪替丁（0.1 - 10微克/2微升，ICV）与硫代酰胺（10毫克/10毫升/千克，IP）或化合物48/80（1.0微克/2微升，ICV）联合处理时，在亮区停留的时间和穿梭次数才显著减少。这些行为参数的降低表明小鼠出现了实验性焦虑。实验性焦虑可被美吡拉敏（10微克/2微升，ICV）拮抗。这些结果表明，不仅硫代酰胺诱导的神经元组胺释放，而且化合物48/80诱导的非神经元（肥大细胞）组胺释放，在通过突触后H(1)和H(2)受体诱导实验性焦虑中起重要作用。此外，焦虑可能由H(1)受体的刺激介导，而H(2)受体可能抑制H(1)受体激活产生的焦虑。
