Piepponen T P, Kivastik T, Katajamäki J, Zharkovsky A, Ahtee L
Department of Pharmacy, University of Helsinki, Finland.
Pharmacol Biochem Behav. 1997 Sep;58(1):275-9. doi: 10.1016/s0091-3057(96)00567-9.
The main purpose of this study was to evaluate the role of mu 1-opioid receptors in morphine reward. Therefore, we studied the ability of a mu 1-selective antagonist, naloxonazine [15 mg/kg intraperitoneally (IP)], to antagonize the conditioned place preference (CPP) induced by morphine [3 mg/kg subcutaneously (SC)]. In addition, effects of naloxonazine on morphine-induced catalepsy (15 mg/kg), analgesia (3 mg/kg), and hyperthermia (3 mg/kg) were studied. For comparison, the effects of a nonselective opioid receptor antagonist, naltrexone (2.5 mg/kg SC), and a selective delta-opioid receptor antagonist, naltrindole (2 mg/kg IP), on CPP induced by morphine were investigated. Morphine-induced CPP was clearly antagonized by pretreatment with naloxonazine and naltrexone (12 h and 20 min prior to morphine, respectively) but not by naltrindole (15 min before morphine). Naloxonazine also antagonized morphine-induced catalepsy and analgesia but not morphine-induced hyperthermia. Naltrindole did not modify morphine-induced catalepsy. These results suggest an active role for mu 1-opioid receptors in morphine reward, whereas morphine-induced hyperthermia does not appear to be mediated by mu 1-opioid receptors. Furthermore, delta-opioid receptors seem to be without significance in morphine-induced reward.
本研究的主要目的是评估μ1阿片受体在吗啡奖赏中的作用。因此,我们研究了μ1选择性拮抗剂纳洛嗪(腹腔注射15mg/kg)拮抗吗啡(皮下注射3mg/kg)诱导的条件性位置偏爱(CPP)的能力。此外,还研究了纳洛嗪对吗啡诱导的僵住症(15mg/kg)、镇痛(3mg/kg)和体温过高(3mg/kg)的影响。为作比较,研究了非选择性阿片受体拮抗剂纳曲酮(皮下注射2.5mg/kg)和选择性δ阿片受体拮抗剂纳曲吲哚(腹腔注射2mg/kg)对吗啡诱导的CPP的影响。纳洛嗪和纳曲酮预处理(分别在给予吗啡前12小时和20分钟)可明显拮抗吗啡诱导的CPP,但纳曲吲哚预处理(在给予吗啡前15分钟)则不能。纳洛嗪还可拮抗吗啡诱导的僵住症和镇痛,但不能拮抗吗啡诱导的体温过高。纳曲吲哚不改变吗啡诱导的僵住症。这些结果表明μ1阿片受体在吗啡奖赏中发挥积极作用,而吗啡诱导的体温过高似乎不是由μ1阿片受体介导的。此外,δ阿片受体在吗啡诱导的奖赏中似乎无作用。