已显示地西泮给药影响与运动行为有关的各种大脑区域中组胺的释放。因此,本研究使用旋转杆和光束行走试验,探讨了中枢组胺能系统在地西泮诱导的小鼠运动表现缺陷中的合理调节作用。在这项研究中,几种剂量的地西泮(0.5、1、2和3mg/kg,i.p.)在旋转杆和光束行走测试中评估小鼠的运动性能变化。此外,服用地西泮后测定脑内组胺水平,并在小鼠中评估地西泮诱导的运动缺陷,用组胺能药物如组胺(0.1,10µg)进行中央预处理(侧脑室),组胺前体(L-组氨酸:0.1,2.5µg),组胺神经元释放剂/H3受体拮抗剂(硫过酰胺:0.5,10µg),H1和H2受体激动剂[2-(3-三氟甲基苯基)组胺(FMPH:0.1,6.5µg;氨甲胺:0.1,5µg)/拮抗剂(H1:西替利嗪0.1µg)和(H2:雷尼替丁:50µg)]。结果表明,以剂量1、2mg/kg的地西泮治疗的小鼠,i.p.显著增加脑组胺水平。此外,在用组胺能传递增强剂预处理的小鼠中,地西泮(2毫克/千克,i.p.)引起的运动不协调显着逆转。相反,地西泮(1mg/kg,i.p.)在两种使用的测试中,均在侧脑室前注射了组胺H1和H2受体拮抗剂的小鼠中产生了明显的运动缺陷。因此,据推测,内源性组胺通过H1和H2受体激活起作用,以减轻地西泮的运动障碍作用。
Diazepam administration has been shown to influence the release of histamine in various brain areas involved in motor behavior. Therefore, the present study explored the plausible regulatory role of the central histaminergic system in diazepam-induced deficits in motor performance in mice using the rota-rod and beam walking tests. In this study, several doses of
diazepam (0.5, 1, 2, and 3 mg/kg, i.p.) were assessed in mice for changes in motor performance on the rota-rod and beam walking test. In addition, the brain histamine levels were determined after
diazepam administration, and the
diazepam-induced motor deficits were assessed in mice, pretreated centrally (intracerebroventricular) with histaminergic agents such as histamine (0.1, 10 µg), histamine precursor (L-histidine: 0.1, 2.5 µg), histamine neuronal releaser/H 3 receptor antagonist (thioperamide: 0.5, 10 µg), H 1 and H 2 receptor agonist [2-(3-trifluoromethylphenyl) histamine (FMPH: 0.1, 6.5 µg; amthamine: 0.1, 5 µg)/antagonist (H 1 : cetirizine 0.1 µg) and (H 2 : ranitidine: 50 µg)]. Results indicate that mice treated with diazepam at doses 1, 2 mg/kg, i.p. significantly increased the brain histamine levels. Moreover, in mice pretreated with histaminergic transmission-enhancing agents, the
diazepam (2 mg/kg, i.p.)-induced motor incoordination was significantly reversed. Contrastingly,
diazepam (1 mg/kg, i.p.) in its subeffective dose produced significant motor deficits in mice preintracerebroventricular injected with histamine H 1 and H 2 receptor antagonists on both the employed tests. Therefore, it is postulated that endogenous histamine operates via H 1 and H 2 receptor activation to alleviate the motor-impairing effects of diazepam.