Department of Pharmacology, Institute of Pharmaceutical Sciences, Guru Ghasidas University (A Central University), Koni, Bilaspur, Chhattisgarh, 495009, India.
Department of Pharmacology, Institute of Pharmaceutical Sciences, Guru Ghasidas University (A Central University), Koni, Bilaspur, Chhattisgarh, 495009, India.
Behav Brain Res. 2021 Feb 5;399:112997. doi: 10.1016/j.bbr.2020.112997. Epub 2020 Nov 6.
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. 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 H receptor inverse agonist, thioperamide (2, 10 μg/mouse), histamine H receptor agonist, FMPH (2, 6.5 μg/mouse) or H 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or intraperitoneally (i.p.) with histamine precursor, l-histidine (250, 500 mg/kg) as compared to control nicotine withdrawn animals.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 H 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 H receptor antagonist, cetirizine (0.1 μg/mouse, i.c.v.) or H 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 H or H 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 H or H receptor stimulation in the nicotine withdrawal induced anxiety and somatic behavior is proposed.
本研究探讨了中枢组胺能传递对尼古丁戒断诱导的焦虑和躯体行为表达的调节作用。在第 12 天，突然停止对小鼠进行为期 12 天的慢性尼古丁（2mg/kg，ip×3/天）治疗，导致在尼古丁戒断后 24 小时，在明暗测试和完全戒断（躯体）评分中表现出焦虑增加。躯体症状包括所有行为的综合评分，如梳理、竖起、跳跃、身体颤抖、前肢震颤、摇头、腹部收缩、抓挠、空口咀嚼或牙齿打颤、生殖器舔舐、舔尾。在尼古丁戒断后 24 小时，与对照组相比，预先经中央（icv）给予组胺能药物，如组胺（0.1、50μg/只）、组胺 H 受体反向激动剂噻庚啶（2、10μg/只）、组胺 H 受体激动剂 FMPH（2、6.5μg/只）或 H 受体激动剂氨甲酰胆碱（0.1、0.5μg/只），或腹腔内给予组胺前体 L-组氨酸（250、500mg/kg），小鼠在明暗测试中表现出对尼古丁戒断诱导的焦虑的表达更高。此外，除了组胺 H 受体激动剂 FMPH 外，所有这些组胺能药物预先治疗的小鼠在尼古丁戒断后 24 小时内，对总戒断（躯体）评分的表达加剧。另一方面，在尼古丁戒断后 24 小时，向小鼠预先给予选择性组胺 H 受体拮抗剂西替利嗪（0.1μg/只，icv）或 H 受体拮抗剂雷尼替丁（50μg/只，icv）10 分钟，可以完全缓解尼古丁戒断诱导的焦虑和躯体行为。因此，可以认为在尼古丁戒断阶段阻断中枢组胺 H 或 H 受体可能是减轻与尼古丁戒断相关的焦虑样表现的一种新方法。提出了内源性组胺通过 H 或 H 受体刺激在尼古丁戒断诱导的焦虑和躯体行为中的作用。
