Ciccocioppo R, Angeletti S, Sanna P P, Weiss F, Massi M
Department of Pharmacological Sciences and Experimental Medicine, University of Camerino, Via Scalzino 5, 62032 (MC), Camerino, Italy.
Eur J Pharmacol. 2000 Sep 15;404(1-2):153-9. doi: 10.1016/s0014-2999(00)00590-2.
The present study investigated the effect of nociceptin/orphanin FQ, the endogenous ligand of the opioid receptor-like 1 (ORL1) receptor, on the rewarding properties of morphine in the place conditioning paradigm. Intracerebroventricular (i.c.v.) injections of nociceptin/orphanin FQ, 500 or 1000 (but not 250) ng/rat, abolished conditioned place preference induced by subcutaneous (s.c.) injections of morphine (3 mg/kg). These doses of nociceptin/orphanin FQ induced neither place aversion nor preference per se. The same doses did not modify the rat performance in the Morris water test, suggesting that they do not disrupt spatial learning and memory. Moreover, these doses of nociceptin/orphanin FQ did not modify the development of morphine-induced locomotor sensitization, suggesting that they do not interfere with sensitization processes to morphine. The present results confirm and extend previous reports that nociceptin/orphanin FQ is able to abolish morphine-induced conditioned place preference, and raise interest for the possible role of nociceptin/orphanin FQ and ORL1 receptors in the control of opiate abuse.
本研究在条件性位置偏爱范式中，探究了阿片受体样1（ORL1）受体的内源性配体孤啡肽对吗啡奖赏特性的影响。脑室内（i.c.v.）注射500或1000 ng/大鼠（而非250 ng/大鼠）的孤啡肽，可消除皮下（s.c.）注射吗啡（3 mg/kg）诱导的条件性位置偏爱。这些剂量的孤啡肽本身既不诱导位置厌恶也不诱导位置偏爱。相同剂量并未改变大鼠在莫里斯水迷宫实验中的表现，表明它们不会破坏空间学习和记忆。此外，这些剂量的孤啡肽并未改变吗啡诱导的运动敏化的发展，表明它们不会干扰对吗啡的敏化过程。本研究结果证实并扩展了先前的报道，即孤啡肽能够消除吗啡诱导的条件性位置偏爱，并引发了对孤啡肽和ORL1受体在阿片类药物滥用控制中可能作用的关注。
