Rezvani Amir H, Tizabi Yousef, Slade Susan, Getachew Bruk, Levin Edward D
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, 27710, USA.
Department of Pharmacology, Howard University, Washington DC, 20059, USA.
Neurosci Lett. 2018 Mar 6;668:98-102. doi: 10.1016/j.neulet.2018.01.022. Epub 2018 Jan 12.
Smoking cessation strategies are of prime medical importance. Despite availability of various pharmacological agents in combating addiction to nicotine, more effective medications are needed. Based on recent findings, the glutamatergic system in the brain may provide novel targets. Here, we evaluated the effects of acute administration of sub-anesthetic doses of ketamine, an NMDA receptor antagonist, in both male and female Sprague-Dawley rats trained to self-administer nicotine. Animals were injected subcutaneously with 5, 7.5 and 10 mg/kg ketamine or saline and the effects on the number of intravenous nicotine infusions during a 45 min session was measured. Ketamine treatment significantly reduced nicotine self-administration in a dose-dependent manner. Moreover, a differential sensitivity between the sexes was observed as male rats responded to a lower dose of ketamine and with higher magnitude of effect than female rats. It is concluded that glutamatergic receptor manipulations may offer a novel and potentially sex-dependent intervention in nicotine addiction.
戒烟策略具有至关重要的医学意义。尽管有多种药物可用于对抗尼古丁成瘾，但仍需要更有效的药物。基于最近的研究结果，大脑中的谷氨酸能系统可能提供新的靶点。在此，我们评估了在经过训练可自行注射尼古丁的雄性和雌性Sprague-Dawley大鼠中，急性给予亚麻醉剂量的氯胺酮（一种NMDA受体拮抗剂）的效果。给动物皮下注射5、7.5和10mg/kg氯胺酮或生理盐水，并测量在45分钟期间对静脉注射尼古丁次数的影响。氯胺酮治疗以剂量依赖的方式显著减少了尼古丁的自我给药。此外，观察到两性之间存在差异敏感性，因为雄性大鼠对较低剂量的氯胺酮有反应，且其效果的程度高于雌性大鼠。结论是，谷氨酸能受体操纵可能为尼古丁成瘾提供一种新的、可能与性别有关的干预措施。
