Shahzadi Andleeb, Uskur Tuğçe, Akkan A Gökhan, Çevreli Burcu, Uzbay Tayfun
a Institute of Health Science, Department of Medical Pharmacology, Cerrahpasa Medical Faculty , Istanbul University , Istanbul , Turkey.
b Neuropsychopharmacology Application and Research Center (NPARC) , Üsküdar University , Istanbul , Turkey.
Am J Drug Alcohol Abuse. 2018;44(2):167-174. doi: 10.1080/00952990.2017.1344681. Epub 2017 Jul 27.
Drug-induced conditioned place preference (CPP) is linked to the addictive properties of the drug used. The number of studies that have investigated the effects of propofol on CPP is limited. Research findings suggest that nitric oxide (NO) might play an important role in substance use disorders.
The present study sought to investigate the role of the nitrergic system on the rewarding effects of propofol by using the CPP protocol in rats.
The experiment followed habituation, pre-conditioning, conditioning, and post conditioning sessions. Male Wistar albino rats weighing 240-290 g were divided into eight groups: control (saline), propofol (10, 20, and 40 mg/kg), the NO synthase (NOS) inhibitor N-nitro-L-arginine methyl ester (L-NAME) alone (30 and 60 mg/kg), and in combination with propofol (30 and 60 mg/kg L-NAME plus 40 mg/kg propofol) (n = 8 for each group). The CPP effects of propofol, L-NAME, saline, and their combinations were evaluated. All the drug and saline administrations were performed by intraperitoneal (ip) injections.
Propofol (10-40 mg/kg) produced CPP that was statistically significant relative to saline. Propofol-induced CPP was significantly reversed by pretreatment with L-NAME. When administered alone, L-NAME did not produce CPP and also did not produce any significant change on locomotor activity of naïve rats.
Our results suggest that propofol produces CPP effects in rats and that NO-related mechanisms may be responsible for propofol-induced CPP. Thus, propofol might have the potential to be addictive, and this possibility should be considered during clinical applications of this drug.
药物诱导的条件性位置偏爱（CPP）与所用药物的成瘾特性有关。研究丙泊酚对CPP影响的研究数量有限。研究结果表明，一氧化氮（NO）可能在物质使用障碍中起重要作用。
本研究旨在通过在大鼠中使用CPP实验方案来探究氮能系统在丙泊酚奖赏效应中的作用。
实验依次包括习惯化、预条件化、条件化和后条件化阶段。将体重240 - 290克的雄性Wistar白化大鼠分为八组：对照组（生理盐水）、丙泊酚组（10、20和40毫克/千克）、一氧化氮合酶（NOS）抑制剂L-硝基精氨酸甲酯（L-NAME）单独给药组（30和60毫克/千克）以及与丙泊酚联合给药组（30和60毫克/千克L-NAME加40毫克/千克丙泊酚）（每组n = 8）。评估丙泊酚、L-NAME、生理盐水及其组合的CPP效应。所有药物和生理盐水均通过腹腔注射给药。
丙泊酚（10 - 40毫克/千克）产生了相对于生理盐水具有统计学意义的CPP。L-NAME预处理可显著逆转丙泊酚诱导的CPP。单独给药时，L-NAME未产生CPP，对未处理大鼠的运动活动也未产生任何显著变化。
我们的结果表明丙泊酚在大鼠中产生CPP效应，且与NO相关的机制可能是丙泊酚诱导CPP的原因。因此，丙泊酚可能具有成瘾潜力，在该药物的临床应用中应考虑到这种可能性。
