Uslaner Jason M, Winrow Christopher J, Gotter Anthony L, Roecker Anthony J, Coleman Paul J, Hutson Pete H, Le Anh D, Renger John J
Departments of Pharmacology, Merck & Co., Inc., West Point, PA 19486, USA.
Departments of Neuroscience, Merck & Co., Inc., West Point, PA 19486, USA.
Behav Brain Res. 2014 Aug 1;269:61-5. doi: 10.1016/j.bbr.2014.04.012. Epub 2014 Apr 18.
The orexinergic system has been implicated in a number of behaviors, including reward and incentive motivation. Orexin 1 receptor antagonism has been reported to reduce drug self-administration, conditioned place preference, and reinstatement in rodents, but the role of the orexin 2 receptor is unclear. Here we evaluated the impact of the novel and selective orexin 2 receptor antagonist, 2-SORA 18, on motivation for nicotine as measured by responding on a progressive ratio schedule, as well as cue-induced reinstatement of a response previously associated with nicotine reward, and nicotine-induced reinstatement. 2-SORA 18 demonstrated selective effects on these behaviors. Specifically, doses up to 60 mg/kg 2-SORA 18 were without significant effect on nicotine self-administration or nicotine-induced reinstatement, but doses as low as 15 mg/kg 2-SORA 18 completely blocked cue-induced reinstatement. These findings indicate that orexin 2 receptor antagonism might have utility for attenuating relapse, particularly for patients sensitive to environmental stimuli associated with drug taking.
食欲素能系统与多种行为有关，包括奖赏和动机激励。据报道，食欲素1受体拮抗剂可减少啮齿动物的药物自我给药、条件性位置偏爱和复吸，但食欲素2受体的作用尚不清楚。在此，我们评估了新型选择性食欲素2受体拮抗剂2-SORA 18对尼古丁动机的影响，该影响通过在累进比率程序上的反应来衡量，以及线索诱导的先前与尼古丁奖赏相关的反应复吸和尼古丁诱导的复吸。2-SORA 18对这些行为表现出选择性作用。具体而言，高达60mg/kg的2-SORA 18剂量对尼古丁自我给药或尼古丁诱导的复吸无显著影响，但低至15mg/kg的2-SORA 18剂量可完全阻断线索诱导的复吸。这些发现表明，食欲素2受体拮抗作用可能对减轻复吸有用，特别是对于对与吸毒相关的环境刺激敏感的患者。
