Rezvani Amir H, Cauley Marty C, Slade Susan, Wells Corinne, Glick Stanley, Rose Jed E, Levin Edward D
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, USA.
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, USA.
Pharmacol Biochem Behav. 2016 Nov-Dec;150-151:153-157. doi: 10.1016/j.pbb.2016.10.010. Epub 2016 Oct 29.
The ibogaine derivative 18-methoxycoronaridine (18-MC) has been found to decrease self-administration of morphine, nicotine and alcohol in rats after systemic injection. However oral dosing is the preferred route clinically. The current study evaluated the effect of oral 18-MC dosing in rats on alcohol and nicotine self-administration. For the nicotine study, young adult female Sprague-Dawley rats were fitted with IV jugular infusion catheters and trained for nicotine self-administration in 45min. sessions. At weekly intervals they were administered by oral gavage doses of 18-MC (0, 10, 20 and 40mg/kg) following a repeated measures counterbalanced design twice. Acute oral 18-MC, at the 40mg/kg dosage, significantly reduced nicotine self-administration. There was a differential effect of 18-MC with rats above or below the median level of nicotine self-administration during the pretreatment baseline performance. Rats with lower baseline performance showed a significant reduction in nicotine self-administration with the 40mg/kg dosage, while those in the higher baseline group did not show a significant effect of 18-MC. In alcohol studies, the effects of the same doses of 18-MC were tested in both male and female alcohol preferring (P) rats that had free access to water and alcohol (10% v/v) 6h/day. The results show that 18-MC dose-dependently reduced alcohol intake in both male and female rats. All doses caused significant reductions in alcohol self-administration. These data reinforce previous findings that 18-MC is significantly effective in reducing alcohol intake and nicotine self-administration. The finding that 18-MC is also effective orally makes it advantageous for further development as a possible new therapy for treating alcoholism as well as smoking addiction.
已发现伊博格碱衍生物18-甲氧基冠狗牙花定碱（18-MC）经全身注射后可减少大鼠对吗啡、尼古丁和酒精的自我给药量。然而，口服给药是临床上更优选的途径。当前研究评估了大鼠口服18-MC对酒精和尼古丁自我给药的影响。在尼古丁研究中，给年轻成年雌性斯普拉格-道利大鼠植入颈静脉输液导管，并训练它们在45分钟的时间段内进行尼古丁自我给药。按照重复测量平衡设计，每周两次通过灌胃给它们施用18-MC（0、10、20和40mg/kg）剂量。40mg/kg剂量的急性口服18-MC显著减少了尼古丁自我给药量。在预处理基线表现期间，18-MC对尼古丁自我给药量处于中位数水平之上或之下的大鼠有不同影响。基线表现较低的大鼠在40mg/kg剂量下尼古丁自我给药量显著减少，而基线水平较高组的大鼠未显示18-MC有显著作用。在酒精研究中，对可自由获取水和酒精（10% v/v，每天6小时）的雄性和雌性嗜酒（P）大鼠测试了相同剂量的18-MC的效果。结果表明，18-MC剂量依赖性地减少了雄性和雌性大鼠的酒精摄入量。所有剂量均显著减少了酒精自我给药量。这些数据强化了先前的研究结果，即18-MC在减少酒精摄入量和尼古丁自我给药量方面显著有效。18-MC口服也有效的这一发现使其有利于作为治疗酒精中毒以及吸烟成瘾的一种可能的新疗法进一步开发。
