Martin J R, Takemori A E
Eur J Pharmacol. 1985 Dec 10;119(1-2):75-84. doi: 10.1016/0014-2999(85)90324-3.
Acute administration of an opiate has been suggested to result in the development of supersensitive dopamine receptors. This hypothesis was tested in mice by determining the effect of a single administration of morphine or levorphanol on dopamine agonist-induced stereotypic behaviors and [3H]spiroperidol binding. Administration of morphine (1.0 mg/kg s.c.), which itself had no significant effect on spontaneous locomotor activity 3 h following administration, significantly potentiated locomotor activity induced by 1.5 or 4.5 mg/kg of apomorphine (i.p.) administered 3 h later. Morphine (10 mg/kg, s.c.) or levorphanol (0.2 and 2.0 mg/kg, s.c.), but not dextrorphan (up to 20 mg/kg, s.c.), enhanced climbing behavior induced by apomorphine (i.p.) or (-)-N-n-propylnorapomorphine (i.p.; NPA) administered 3 h later. An increase in whole brain and striatal [3H]spiroperidol binding sites was found 3 h after administration of 10 mg/kg of morphine. Concurrent administration of 5 mEq/kg of LiCl (i.p.) or 5 mg/kg of naloxone (i.p.; administered twice) attenuated both the potentiation of the climbing behavior induced by the two dopamine agonists and the increase in [3H]spiroperidol binding sites. These results suggest that a single administration of an opiate can induce the development of supersensitive dopamine receptors that is mediated by an interaction at opioid receptors.
有人提出，急性给予阿片类药物会导致多巴胺受体超敏。通过测定单次给予吗啡或左啡诺对多巴胺激动剂诱导的刻板行为和[3H]螺哌啶醇结合的影响，在小鼠中对这一假说进行了验证。给予吗啡（1.0mg/kg，皮下注射），给药后3小时其本身对自发运动活动无显著影响，但显著增强了3小时后腹腔注射1.5或4.5mg/kg阿扑吗啡诱导的运动活动。吗啡（10mg/kg，皮下注射）或左啡诺（0.2和2.0mg/kg，皮下注射），但不是右啡烷（高达20mg/kg，皮下注射），增强了3小时后腹腔注射阿扑吗啡或（-）-N-正丙基去甲阿扑吗啡（腹腔注射；NPA）诱导的攀爬行为。给予10mg/kg吗啡3小时后，发现全脑和纹状体[3H]螺哌啶醇结合位点增加。腹腔注射5mEq/kg LiCl或5mg/kg纳洛酮（腹腔注射，给药两次）可同时减弱两种多巴胺激动剂诱导的攀爬行为增强和[3H]螺哌啶醇结合位点的增加。这些结果表明，单次给予阿片类药物可诱导多巴胺受体超敏的发生，这是由阿片受体的相互作用介导的。
