Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Staszica 4, PL20-081 Lublin, Poland.
Pharmacol Rep. 2010 Sep-Oct;62(5):797-807. doi: 10.1016/s1734-1140(10)70340-6.
The present study focused on the evaluation of behavioral sensitization, cross-sensitization, and cross-reinstatement processes induced by nicotine and ethanol in rodents. First, we showed that nicotine (0.175 mg/kg, base, intraperitoneally, ip) produced a conditioned place preference in rats. When the nicotine place preference was extinguished, nicotine-experienced animals were challenged with nicotine (0.175 mg/kg, ip) or ethanol (0.5 g/kg, ip), which reinstated a preference for the compartment previously paired with nicotine. In the second series of experiments, we demonstrated that after 9 days of nicotine administration (0.175 mg/kg, subcutaneously, sc) every other day and following its 7-day withdrawal, challenge doses of nicotine (0.175 mg/kg, sc) and ethanol (2 g/kg, ip) induced locomotor sensitization in mice. Finally, when we examined the influence of rimonabant (0.5, 1 and 2 mg/kg, ip), we found that this cannabinoid CB₁ receptor antagonist attenuated reinstatement effect of ethanol priming as well as nicotine sensitization and locomotor cross-sensitization between nicotine and ethanol. Our results indicate that similar endocannabinoid-dependent mechanisms re involved in the locomotor stimulant and reinforcing effects of nicotine and ethanol in rodents, and as such these data may provide further evidence for the use of cannabinoid CB₁ receptor antagonists in treatment of tobacco addiction with or without concomitant ethanol dependence.
本研究专注于评估尼古丁和乙醇在啮齿动物中引起的行为敏化、交叉敏化和交叉复吸过程。首先，我们表明尼古丁（0.175mg/kg，碱，腹腔内注射，ip）在大鼠中产生了条件性位置偏好。当尼古丁的位置偏好被消除后，接受过尼古丁处理的动物会受到尼古丁（0.175mg/kg，ip）或乙醇（0.5g/kg，ip）的挑战，这会重新引起对以前与尼古丁配对的隔间的偏好。在第二组实验中，我们证明，在每天接受 9 天的尼古丁（0.175mg/kg，皮下注射，sc）治疗后，以及在其 7 天的戒断后，尼古丁（0.175mg/kg，sc）和乙醇（2g/kg，ip）的挑战剂量会在小鼠中引起运动敏化。最后，当我们检查利莫那班（0.5、1 和 2mg/kg，ip）的影响时，我们发现这种大麻素 CB₁受体拮抗剂减弱了乙醇引发的复吸效应，以及尼古丁敏化和尼古丁与乙醇之间的运动交叉敏化。我们的结果表明，类似的内源性大麻素依赖机制参与了尼古丁和乙醇在啮齿动物中的运动刺激和强化作用，因此这些数据可能为使用大麻素 CB₁受体拮抗剂治疗烟草成瘾提供进一步证据，无论是否伴有乙醇依赖。
