Discriminative stimulus effects of morphine: central versus peripheral training.
Discriminative stimulus effects of morphine: central versus peripheral training.
复制标题
吗啡的辨别刺激作用：中枢与外周训练。
DOI：
10.1016/s0006-8993(99)02001-6
复制
发表时间：
1999
期刊：
影响因子：
2.9
通讯作者：
Levine,AS
中科院分区：
文献类型：
--
作者：
Cleary,JP;O'Hare,E;Pomonis,JD;Dittel,PL;Hofmeister,JJ;Fritz,MM;Billington,CJ;Levine,AS
众所周知，大鼠可以区分外周注射的吗啡和生理盐水注射，但据我们所知，还没有人训练大鼠区分脑内直接注射的吗啡和生理盐水。在目前的一系列研究中，一组大鼠被训练区分吗啡（0.3 μg）和注入下丘脑皮层周围区（PFA）的生理盐水，这一过程需要大鼠大约37次的学习。在pfa注射吗啡（0.01、0.03、0.1和0.17 μg）的剂量反应泛化曲线上，两个最高剂量的吗啡被一般化到吗啡适宜性训练刺激上。腹腔注射吗啡3mg /kg，而不是1mg /kg，在PFA吗啡训练大鼠中产生吗啡适当反应。第二组大鼠被训练以区分静脉注射3 mg/kg吗啡和生理盐水。采用0.3、0.56、1.0和1.7 mg/kg吗啡注射组进行剂量反应泛化试验，其中0.17 mg/kg吗啡泛化到吗啡适宜性训练刺激。采用pfa注射吗啡剂量（0.17、0.56、1.0和3.0 μg）的泛化试验未能在吗啡训练大鼠中产生吗啡适宜性反应。给予PFA （50 μg）或外周（3 mg/kg, i.p）纳洛酮阻断了PFA训练大鼠对吗啡的识别。然而，当纳洛酮（50 μg）与静脉注射吗啡（3 mg/kg）一起注射到经静脉注射训练的动物PFA时，拮抗剂未能阻断吗啡适当反应。因此，虽然外周注射吗啡推广到pfa注射训练下产生的吗啡的鉴别刺激作用，但没有注意到相反的作用。
While it is well known that rats can discriminate a peripheral injection of morphine from a saline injection, to our knowledge no one has trained rats to discriminate a direct brain-site injection of morphine from saline. In the present series of studies, one group of rats was trained to discriminate morphine (0.3 μg) from saline injected into the perifornical area of the hypothalamus (PFA), a process that took rats about 37 sessions to learn. A dose response generalization curve for PFA-injected morphine (0.01, 0.03, 0.1, and 0.17 μg) was generated in which the two highest doses of morphine generalized to the morphine-appropriate training stimulus. Intraperitoneal (i.p.) injection of 3 mg/kg, but not 1 mg/kg morphine, resulted in morphine-appropriate responding in the PFA morphine-trained rats. A second group of rats was trained to discriminate i.p. injections of 3 mg/kg morphine from injections of saline. A dose–response generalization test for i.p.-injected morphine (0.3, 0.56, 1.0, and 1.7 mg/kg) was conducted in which the 0.17 mg/kg dose of morphine generalized to the morphine-appropriate training stimulus. Generalization tests using PFA-injected morphine doses (0.17, 0.56, 1.0, and 3.0 μg) failed to result in morphine-appropriate responding in the i.p. morphine-trained rats. Naloxone administered into the PFA (50 μg) or the periphery (3 mg/kg, i.p.) blocked morphine discrimination in the PFA-trained rats. However, when naloxone was injected into the PFA (50 μg) together with i.p. morphine (3 mg/kg) in animals trained using i.p. injections, the antagonist failed to block morphine-appropriate responding. Thus, while peripheral injection of morphine generalized to the discriminative stimulus effects of morphine produced under PFA-injection training, the opposite effects were not noted.