Schindler C W, Gormezano I, Harvey J A
National Institute on Drug Abuse, Addiction Research Center, Baltimore, Maryland.
J Pharmacol Exp Ther. 1987 Dec;243(3):1010-7.
A series of five experiments examined the effects of mu and kappa opioid agonists on acquisition of conditioned responses in the rabbit and the antagonism of their effects by naloxone. Extension of the nictitating membrane was classically conditioned to a tone stimulus presented before delivery of an electric shock unconditioned stimulus to the skin over the paraorbital region of the head. Morphine, ethylketocyclazocine and U-50,488H retarded the acquisition of conditioned responses to the tone conditioned stimulus with ethylketocyclazocine being twice as potent as the more specific kappa agonist U-50,488H, and 40 times more potent than the prototypic mu agonist morphine. Control experiments indicated that the retarded acquisition produced by the three opioids was due to an action on associative learning. Doses of 0.1 and 1.0 mg/kg of naloxone alone did not affect acquisition of conditioned responses, but did significantly antagonize the retardant effects of all three opioid agonists. On the basis of the parallelism of the dose-effect curves for the three opioid agonists, their order of potency which was remarkably different from potency ratios observed for other measures, e.g. analgesia, and on the finding that all three opioids demonstrated approximately equivalent sensitivity to antagonism by naloxone, it was concluded that the effects of all three opioid agonists on the acquisition of conditioned responses may be mediated by a common receptor.
一系列五项实验研究了μ和κ阿片样物质激动剂对家兔条件反应习得的影响以及纳洛酮对其作用的拮抗作用。将瞬膜的伸展通过经典条件反射训练，使其与在对头眶周区域皮肤给予电击非条件刺激之前呈现的音调刺激相关联。吗啡、乙基酮环唑新和U-50,488H延缓了对音调条件刺激的条件反应的习得，其中乙基酮环唑新的效力是更具特异性的κ激动剂U-50,488H的两倍，比原型μ激动剂吗啡强40倍。对照实验表明，这三种阿片样物质产生的习得延缓是由于对联想学习的作用。单独使用0.1和1.0mg/kg的纳洛酮剂量不影响条件反应的习得，但确实显著拮抗了所有三种阿片样物质激动剂的延缓作用。基于三种阿片样物质激动剂剂量-效应曲线的平行性、它们的效力顺序（与其他指标如镇痛所观察到的效力比值显著不同）以及所有三种阿片样物质对纳洛酮拮抗作用表现出大致相同的敏感性这一发现，得出结论：所有三种阿片样物质激动剂对条件反应习得的作用可能由一种共同的受体介导。
