Pérez-García C, Morales L, Cano M V, Sancho I, Alguacil L F
Laboratory of Pharmacology, University of San Pablo CEU, Madrid, Spain.
Psychopharmacology (Berl). 1999 Feb;142(2):215-20. doi: 10.1007/s002130050882.
Histamine H3 receptor ligands have been proposed to be of potential therapeutic interest for the treatment of different central nervous system disorders; however, the psychopharmacological properties of these drugs have not been studied extensively. In this work, we investigated the possible involvement of histamine H3 receptor function in experimental models of anxiety (elevated plus-maze) and depression (forced swimming test). Male Sprague-Dawley rats were treated i.p. with the histamine H3 receptor agonist R-alpha-methylhistamine (10 mg/kg) or the histamine H3 receptor antagonist thioperamide (0.2, 2 and 10 mg/kg) and 30 min afterwards the time spent in the open arms of an elevated plus-maze was registered for 5 min. The immobility time of male OF1 mice in the forced swimming test was recorded for 6 min, 1 h after the i.p. administration of R-alpha-methylhistamine (10 and 20 mg/kg), thioperamide (0.2, 2, 10 and 20 mg/kg) or another histamine H3 receptor antagonist, clobenpropit (5 mg/kg). The locomotor activity of mice was checked in parallel by means of an activity meter. Both saline controls and active drug controls were used in all the paradigms. Neither thioperamide nor R-alpha-methylhistamine significantly changed animal behaviour in the elevated plus-maze. R-alpha-methylhistamine and the higher dose of thioperamide assayed (20 mg/kg) were also inactive in the forced swimming test. By contrast, thioperamide (0.2-10 mg/kg) dose-dependently decreased immobility, the effect being significant at 10 mg/kg (33% reduction of immobility); clobenpropit produced an effect qualitatively similar (24% reduction of immobility). None of these histamine H3 receptor antagonists affected locomotor activity. These preliminary results suggest that the histamine H3 receptor blockade could be devoid of anxiolytic potential but have antidepressant effects. Besides, the stimulation of these receptors does not seem to be followed by changes in the behavioural parameters studied.
组胺H3受体配体已被认为对治疗不同的中枢神经系统疾病具有潜在的治疗意义；然而，这些药物的精神药理学特性尚未得到广泛研究。在这项研究中，我们研究了组胺H3受体功能在焦虑（高架十字迷宫）和抑郁（强迫游泳试验）实验模型中可能的作用。雄性Sprague-Dawley大鼠腹腔注射组胺H3受体激动剂R-α-甲基组胺（10mg/kg）或组胺H3受体拮抗剂硫代哌酰胺（0.2、2和10mg/kg），30分钟后记录其在高架十字迷宫开放臂中停留的时间，持续5分钟。在腹腔注射R-α-甲基组胺（10和20mg/kg）、硫代哌酰胺（0.2、2、10和20mg/kg）或另一种组胺H3受体拮抗剂氯苯丙哌嗪（5mg/kg）1小时后，记录雄性OF1小鼠在强迫游泳试验中的不动时间，持续6分钟。同时，通过活动计检查小鼠的运动活性。在所有实验范式中均使用生理盐水对照组和活性药物对照组。硫代哌酰胺和R-α-甲基组胺在高架十字迷宫中均未显著改变动物行为。R-α-甲基组胺和所检测的较高剂量硫代哌酰胺（20mg/kg）在强迫游泳试验中也无活性。相比之下，硫代哌酰胺（0.2-10mg/kg）剂量依赖性地减少不动时间，在10mg/kg时效果显著（不动时间减少33%）；氯苯丙哌嗪产生了定性相似的效果（不动时间减少24%）。这些组胺H3受体拮抗剂均未影响运动活性。这些初步结果表明，组胺H3受体阻断可能没有抗焦虑作用，但具有抗抑郁作用。此外，刺激这些受体似乎不会导致所研究的行为参数发生变化。
