Center for Drug Discovery, RTI International, 3040 Cornwallis Rd, Research Triangle Park, NC 27709, USA.
Center for Drug Discovery, RTI International, 3040 Cornwallis Rd, Research Triangle Park, NC 27709, USA.
Pharmacol Biochem Behav. 2023 Oct;231:173632. doi: 10.1016/j.pbb.2023.173632. Epub 2023 Sep 9.
The co-use of nicotine and cannabis has been steadily rising in the United States. Rodent studies suggest that delta-9-tetrahydrocannabinol (THC) could increase addictive qualities of nicotine, but whether repeated THC exposure alters self-administration of nicotine has not been tested. We hypothesized that THC would increase the reinforcing effects of nicotine and alter nicotine intake.
Adult male and female Sprague-Dawley rats were treated with THC (0, 3, 30 mg/kg) daily for 14 days prior to and during training for intravenous self-administration of nicotine. Rats were allowed to self-administer nicotine for several weeks, then tested for sensitivity to nicotine dose through multiple determinations of a nicotine dose-effect curve with or without THC pretreatment. A separate set of rats were trained on fixed ratio responding for sucrose and assessed for THC effects on behavior.
Post-session THC decreased nicotine self-administration in male and female rats throughout acquisition and maintenance and increased the latency to stable rates of nicotine intake during acquisition. Post-session THC shifted nicotine dose-effect curves downward, and pre-session THC suppressed responding at higher nicotine doses. Unlike nicotine, responding for sucrose was not affected by post-session THC. Pre-session THC decreased responding for sucrose, particularly for THC-naïve rats.
Repeated post-session THC decreased nicotine-taking behaviors but did not alter sucrose responding. Thus, post-session THC may alter sensitivity to nicotine. Pre-session THC treatment decreased lever pressing in both sucrose and nicotine studies, indicating this effect was nonspecific. These studies show that THC modulates patterns of nicotine intake in rat models.
在美国,尼古丁和大麻的联合使用一直在稳步上升。啮齿动物研究表明,Δ-9-四氢大麻酚(THC)可能会增加尼古丁的成瘾性,但重复接触 THC 是否会改变尼古丁的自我给药行为尚未得到检验。我们假设 THC 会增加尼古丁的强化效应,并改变尼古丁的摄入量。
成年雄性和雌性 Sprague-Dawley 大鼠在接受 THC(0、3、30mg/kg)每日治疗 14 天之前和期间,接受静脉内尼古丁自我给药的训练。大鼠被允许自我给予尼古丁数周,然后通过多次测定尼古丁剂量-效应曲线来测试对尼古丁剂量的敏感性,或在没有 THC 预处理的情况下进行测试。一组单独的大鼠接受蔗糖固定比率反应的训练,并评估 THC 对行为的影响。
给药后,THC 降低了雄性和雌性大鼠在整个获得和维持期间的尼古丁自我给药,增加了获得期间稳定尼古丁摄入量的潜伏期。给药后,THC 使尼古丁剂量-效应曲线向下移动,而给药前的 THC 抑制了较高尼古丁剂量下的反应。与尼古丁不同,蔗糖的反应不受给药后 THC 的影响。给药前的 THC 降低了蔗糖的反应,特别是对未接触过 THC 的大鼠。
重复给药后,THC 减少了尼古丁的摄取行为,但没有改变蔗糖的反应。因此,给药后 THC 可能会改变对尼古丁的敏感性。给药前的 THC 治疗减少了蔗糖和尼古丁研究中的杠杆按压,表明这种效应是非特异性的。这些研究表明,THC 调节了大鼠模型中尼古丁摄入的模式。