Department of Pharmacology, Chitkara College of Pharmacy, Chitkara University, Rajpura, Patiala, 147002, Punjab, India.
Naunyn Schmiedebergs Arch Pharmacol. 2013 Mar;386(3):197-204. doi: 10.1007/s00210-012-0825-0. Epub 2012 Dec 29.
G protein-coupled receptor kinase 5 is noted to mediate a number of signal transduction cascades involved in the causation of nicotine withdrawal syndrome. Therefore, the present study investigated the effect of Ro 32-0432, a G protein-coupled receptor kinase 5 inhibitor, on propagation of nicotine dependence and resultant withdrawal signs in subchronic nicotine mouse model. Our experimental protocol consisted of administration of nicotine, (2.5 mg/kg, subcutaneously), four times daily for 7 days. In order to precipitate nicotine withdrawal, mice were given one injection of mecamylamine (3 mg/kg, intraperitoneally) 1 h after the last nicotine injection on the test day (day 8). Behavioral observations were made for a period of 30 min immediately after mecamylamine treatment. Withdrawal syndrome was quantitated in terms of a composite withdrawal severity score, jumping frequency, nicotine-induced hyperalgesia by tail flick method, and withdrawal syndrome-related anxiety was assessed by elevated plus maze test results. Ro 32-0432 dose dependently attenuated mecamylamine-induced nicotine withdrawal syndrome in mice. It is concluded that Ro 32-0432 attenuates the propagation of nicotine dependence and reduce withdrawal signs possibly by G protein-coupled receptor kinase 5 activation-linked mechanisms.
G 蛋白偶联受体激酶 5 被认为介导了许多涉及尼古丁戒断综合征发生的信号转导级联反应。因此，本研究调查了 G 蛋白偶联受体激酶 5 抑制剂 Ro 32-0432 对慢性尼古丁小鼠模型中尼古丁依赖的传播和由此产生的戒断症状的影响。我们的实验方案包括每天皮下给予尼古丁（2.5mg/kg）四次，持续 7 天。为了引发尼古丁戒断，在测试日（第 8 天）最后一次尼古丁注射后 1 小时，给予小鼠美加仑胺（3mg/kg，腹腔内）一次注射。在美加仑胺处理后立即进行 30 分钟的行为观察。戒断综合征根据综合戒断严重程度评分、跳跃频率、尾 flick 法测量的尼古丁诱导的痛觉过敏以及高架十字迷宫测试结果评估的戒断综合征相关焦虑来定量。Ro 32-0432 剂量依赖性地减弱了美加仑胺诱导的尼古丁戒断综合征。结论是，Ro 32-0432 通过 G 蛋白偶联受体激酶 5 激活相关机制减弱了尼古丁依赖的传播并减少了戒断症状。
