Berrendero Fernando, Kieffer Brigitte L, Maldonado Rafael
Laboratori de Neurofarmacologia, Facultat de Ciéncies de la Salut i de la Vida, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
J Neurosci. 2002 Dec 15;22(24):10935-40. doi: 10.1523/JNEUROSCI.22-24-10935.2002.
The involvement of mu-opioid receptors in different behavioral responses elicited by nicotine was explored by using mu-opioid receptor knock-out mice. The acute antinociceptive responses induced by nicotine in the tail-immersion and hot-plate tests were reduced in the mutant mice, whereas no difference between genotypes was observed in the locomotor responses. The rewarding effects induced by nicotine were then investigated using the conditioning place-preference paradigm. Nicotine produced rewarding responses in wild-type mice but failed to produce place preference in knock-out mice, indicating the inability of this drug to induce rewarding effects in the absence of mu-opioid receptors. Finally, the somatic expression of the nicotine withdrawal syndrome, precipitated in dependent mice by the injection of mecamylamine, was evaluated. Nicotine withdrawal was significantly attenuated in knock-out mutants when compared with wild-type mice. In summary, the present results show that mu-opioid receptors are involved in the rewarding responses induced by nicotine and participate in its antinociceptive responses and the expression of nicotine physical dependence.
通过使用μ-阿片受体基因敲除小鼠，探讨了μ-阿片受体在尼古丁引发的不同行为反应中的作用。在尾部浸入和热板试验中，尼古丁诱导的急性抗伤害感受反应在突变小鼠中降低，而在运动反应中未观察到基因型之间的差异。然后使用条件性位置偏爱范式研究尼古丁诱导的奖赏效应。尼古丁在野生型小鼠中产生奖赏反应，但在基因敲除小鼠中未能产生位置偏爱，表明该药物在没有μ-阿片受体的情况下无法诱导奖赏效应。最后，评估了通过注射美加明在依赖小鼠中引发的尼古丁戒断综合征的躯体表现。与野生型小鼠相比，基因敲除突变体中的尼古丁戒断明显减轻。总之，目前的结果表明，μ-阿片受体参与尼古丁诱导的奖赏反应，并参与其抗伤害感受反应和尼古丁身体依赖性的表现。
