A single administration with METH (3 mg/kg) induced a hyperlocomotion in male ICR mice. Pretreatment of mice with pitolisant, a histamine H3 receptor antagonist (5 and 10 mg/kg), for 30 min showed a significant reduction of the hyperlocomotion induced by METH, as compared with vehicle (saline)-pretreated subjects. Pretreatment of mice with the histamine H3 receptor antagonists JNJ-10181457 (5 and 10 mg/kg) or conessine (20 mg/kg), also showed similar inhibitory effects on METH-induced hyperlocomotion, similar to pitolisant. No significant change in locomotion was observed in mice pretreated with pitolisant, JNJ-10181457, or conessine alone. The pitolisant (10 mg/kg) action on METH-induced hyperlocomotion was completely abolished by the histamine H1 receptor antagonist pyrilamine (10 mg/kg), but not by the peripherally acting histamine H1 receptor antagonist fexofenadine (20 mg/kg), the brain-penetrating histamine H2 receptor antagonist zolantidine (10 mg/kg), or the brain-penetrating histamine H4 receptor antagonist JNJ-7777120 (40 mg/kg). Pretreatment with a histamine H3 receptor agonist immepip (10 mg/kg) augmented METH--induced behavior, including hyperlocomotion and stereotyped biting, and combined pretreatment with pitolisant (10 mg/kg) significantly attenuated stereotyped biting. These observations suggest that pretreatment with histamine H3 receptor antagonists attenuate METH-induced hyperlocomotion via releasing histamine after blocking H3 receptors, which then bind to the post-synaptic histamine receptor H1 (but not H2 or H4). It is likely that activation of brain histamine systems may be a good strategy for the development of agents, which treat METH abuse and dependence.

中文翻译：

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体内评估组胺 H3 受体拮抗剂对甲基苯丙胺诱导的小鼠运动过度的影响。

METH (3 mg/kg) 的单次给药诱导雄性 ICR 小鼠的过度运动。与载体（盐水）预处理的受试者相比，用 pitolisant（一种组胺 H3 受体拮抗剂（5 和 10 毫克/公斤））预处理小鼠 30 分钟，显示由 METH 诱导的过度运动显着减少。用组胺 H3 受体拮抗剂 JNJ-10181457（5 和 10 mg/kg）或 conessine（20 mg/kg）预处理小鼠，也显示出对 METH 诱导的运动过度的类似抑制作用，类似于 pitolisant。在用 pitolisant、JNJ-10181457 或单独的 conessine 预处理的小鼠中没有观察到运动的显着变化。组胺 H1 受体拮抗剂吡拉敏 (10 mg/kg) 完全消除了 pitolisant (10 mg/kg) 对 METH 诱导的运动过度的作用，但不是通过外周作用组胺 H1 受体拮抗剂非索非那定 (20 mg/kg)、脑穿透组胺 H2 受体拮抗剂唑兰替丁 (10 mg/kg) 或脑穿透组胺 H4 受体拮抗剂 JNJ-7777120 (40 mg/kg)公斤）。用组胺 H3 受体激动剂 immepip (10 mg/kg) 预处理可增强 METH 诱导的行为，包括运动过度和刻板咬合，并与 pitolisant (10 mg/kg) 联合预处理显着减弱刻板咬合。这些观察结果表明，用组胺 H3 受体拮抗剂预处理通过在阻断 H3 受体后释放组胺来减弱 METH 诱导的运动过度，然后组胺与突触后组胺受体 H1（但不是 H2 或 H4）结合。