Singh M E, Verty A N A, McGregor I S, Mallet P E
School of Psychology, University of New England, Armidale, NSW 2351, Australia.
Brain Res. 2004 Nov 12;1026(2):244-53. doi: 10.1016/j.brainres.2004.08.027.
The present study compared the effects of the cannabinoid receptor antagonist SR 141716 on morphine-induced locomotor sensitization (Experiment 1) and conditioned place preference (CPP, Experiment 2) in male albino Wistar rats. In Experiment 1, rats received seven consecutive daily treatments with morphine (10 mg/kg, SC) in combination with either SR 141716 (0, 0.1, 0.5 or 3.0 mg/kg, IP), or naloxone (10 mg/kg, IP). Three days later, all rats were challenged with a lower dose of morphine (5 mg/kg, SC). Rats pre-treated with morphine showed significantly elevated locomotor activity during the challenge session compared to vehicle-pre-treated animals indicating behavioural sensitization. Prior naloxone, but not SR 141716, co-administration with morphine, significantly attenuated the locomotor sensitization observed. In Experiment 2A, SR 141716 (0.1 mg/kg, IP), co-administered during conditioning, significantly attenuated the place preference produced by morphine (4 mg/kg, SC) in a standard unbiased two compartment place conditioning task. In Experiment 2B, the timing of drug administration and drug doses used were altered to be similar to Experiment 1, such that a comparison between the sensitization and CPP paradigms could be made. Thus, rats were conditioned with morphine (10 mg/kg, SC) combined with SR 141716 (0, 0.1, 0.5 or 3.0 mg/kg, IP) and tested for place preference under the influence of morphine (5 mg/kg, SC). SR 141716 attenuated morphine place preference at a dose (3.0 mg/kg) that did not itself affect place conditioning. Morphine also induced locomotor sensitization in the drug-paired compartment in Experiment 2B which was not blocked by any dose of SR 141716. We conclude that CB1 receptor antagonism modulates the rewarding value of opioids, but not the behavioural sensitization induced by chronic opioid administration.
本研究比较了大麻素受体拮抗剂SR 141716对雄性白化Wistar大鼠吗啡诱导的运动敏化（实验1）和条件性位置偏爱（CPP，实验2）的影响。在实验1中，大鼠连续7天每天接受吗啡（10 mg/kg，皮下注射）与SR 141716（0、0.1、0.5或3.0 mg/kg，腹腔注射）或纳洛酮（10 mg/kg，腹腔注射）联合治疗。3天后，所有大鼠均接受较低剂量吗啡（5 mg/kg，皮下注射）的激发。与溶剂预处理的动物相比，预先用吗啡处理的大鼠在激发期的运动活性显著升高，表明行为敏化。预先与吗啡联合使用纳洛酮而非SR 141716，可显著减弱观察到的运动敏化。在实验2A中，在条件反射期间共同给予的SR 141716（0.1 mg/kg，腹腔注射），在标准无偏两室位置条件反射任务中显著减弱了吗啡（4 mg/kg，皮下注射）产生的位置偏爱。在实验2B中，改变给药时间和所用药物剂量，使其与实验1相似，以便能够对敏化和CPP范式进行比较。因此，大鼠用吗啡（10 mg/kg，皮下注射）与SR 141716（0、0.1、0.5或3.0 mg/kg，腹腔注射）进行条件反射，并在吗啡（5 mg/kg，皮下注射）的影响下测试位置偏爱。SR 141716在本身不影响位置条件反射的剂量（3.0 mg/kg）下减弱了吗啡位置偏爱。在实验2B中，吗啡还在药物配对隔室中诱导了运动敏化，而任何剂量的SR 141716均未阻断该敏化。我们得出结论，CB1受体拮抗作用调节阿片类药物的奖赏价值，但不调节慢性阿片类药物给药诱导的行为敏化。
