The present study investigated the plausible modulatory role of central histaminergic transmission on the expression of nicotine withdrawal induced anxiety and somatic behavior in mice. Abrupt cessation of chronic nicotine (2 mg/kg, i.p. × 3/day) treatment for 12 days to mice, expressed increased anxiety in light & dark test and total abstinence (somatic) score at 24 h post nicotine withdrawal time. The somatic signs includes a composite score of all behaviors such as grooming, rearing, jumping, body shakes, forelimb tremors, head shakes, abdominal constrictions, scratching, empty mouth chewing or teeth chattering, genital licking, tail licking. Moreover, mice exhibited higher expression to nicotine withdrawal induced anxiety in light & dark test at 24 h post-nicotine withdrawal time on pre-treatment centrally (i.c.v) with histaminergic agents like histamine (0.1, 50 µg/mouse), histamine H₃ receptor inverse agonist, thioperamide (2, 10 µg/mouse), histamine H₁ receptor agonist, FMPH (2, 6.5 µg/mouse) or H₂ receptor agonist amthamine (0.1, 0.5 µg/mouse) or intraperitoneally (i.p.) with histamine precursor, l-histidine (250, 500 mg/kg) as compared to control nicotine withdrawn animals. Furthermore, mice pre-treated with all these histaminergic agents except histamine H₁ receptor agonist, FMPH shows exacerbated expression to post-nicotine withdrawal induced total abstinence (somatic) score in mice. On the other hand, central injection of selective histamine H₁ receptor antagonist, cetirizine (0.1 µg/mouse, i.c.v.) or H₂ receptor antagonist, ranitidine (50 µg/mouse, i.c.v) to mice 10 min before 24 h post-nicotine withdrawal time completely alleviated the expression of nicotine withdrawal induced anxiety and somatic behavior. Thus, it can be contemplated that the blockade of central histamine H₁ or H₂ receptor during the nicotine withdrawal phase could be a novel approach to mitigate the nicotine withdrawal associated anxiety-like manifestations. Contribution of endogenous histamine via H₁ or H₂ receptor stimulation in the nicotine withdrawal induced anxiety and somatic behavior is proposed.

本研究调查了中枢组胺能传递对尼古丁戒断诱发的小鼠焦虑和躯体行为表达的似是而非的调节作用。对小鼠突然停止慢性尼古丁（2 毫克/千克，腹腔注射 × 3/天）治疗 12 天，在尼古丁戒断时间后 24 小时，在明暗测试和总戒断（躯体）评分中表现出增加的焦虑。躯体体征包括所有行为的综合评分，例如梳理、抬起、跳跃、身体摇晃、前肢颤抖、摇头、腹部收缩、抓挠、空嘴咀嚼或牙齿打颤、舔生殖器、舔尾巴。此外，在尼古丁戒断时间后 24 小时，小鼠在明暗测试中对尼古丁戒断诱导的焦虑表现出更高的表达（ic₃受体反向激动剂、硫哌酰胺（2、10 µg/小鼠）、组胺 H ₁受体激动剂、FMPH（2、6.5 µg/小鼠）或 H ₂受体激动剂苯胺胺（0.1、0.5 µg/小鼠）或腹膜内 (ip) 与组胺前体 L-组氨酸 (250, 500 mg/kg) 与对照尼古丁戒断动物相比。此外，除组胺 H ₁受体激动剂外，用所有这些组胺能药物预处理的小鼠FMPH 显示出在小鼠中尼古丁戒断后诱导的总戒断（躯体）评分加剧的表达。另一方面，中枢注射选择性组胺 H ₁受体拮抗剂西替利嗪（0.1 µg/小鼠，icv）或 H ₂受体拮抗剂，雷尼替丁（50 µg/小鼠，icv）在尼古丁戒断时间后 24 小时前 10 分钟给小鼠完全缓解尼古丁戒断引起的焦虑和躯体行为的表达。因此，可以设想在尼古丁戒断阶段阻断中枢组胺H ₁或H ₂受体可能是减轻尼古丁戒断相关焦虑样表现的新方法。提出了内源性组胺通过 H ₁或 H ₂受体刺激对尼古丁戒断诱发的焦虑和躯体行为的贡献。