Molina V A, Heyser C J, Spear L P
Department of Psychology, Binghamton University, State University of New York 13902-6000.
Eur J Pharmacol. 1994 Jul 21;260(1):57-64. doi: 10.1016/0014-2999(94)90009-4.
Adult male rats were exposed to a chronic variable stress treatment, an animal model of depression, with or without concurrent daily administration of desipramine. Animals given chronic and variable stress were submitted daily to a different stressor following an injection of either saline or desipramine (5 mg/kg, i.p.), whereas control animals were unmanipulated except for the injection process. One day after the last event of the chronic procedure, control and stressed animals were administered saline or morphine (0.75 or 1.5 mg/kg, i.p.) and their locomotion assessed for 90 min. In an additional experiment, 24 h after the last stressor, stressed and control rats were challenged with either saline or one of two higher doses (behaviorally suppressant) of morphine (5 and 10 mg/kg, i.p.). A significantly greater increase in locomotor activity following a low dose (1.5 mg/kg) of morphine was observed in chronically stressed rats as compared to control rats. This potentiated locomotor response to morphine in stressed rats was prevented by desipramine pretreatment. The chronic and variable stress treatment did not modify the sedative response to the high doses of morphine. These data support the suggestion that a chronic and variable stress procedure results in sensitization to the stimulant effect of opioid stimulation, and that pretreatment with the antidepressant agent desipramine blocks the development of this sensitization.
成年雄性大鼠接受慢性可变应激处理，这是一种抑郁症动物模型，同时给予或不给予去甲丙咪嗪每日注射。接受慢性可变应激的动物在注射生理盐水或去甲丙咪嗪（5毫克/千克，腹腔注射）后，每天接受不同的应激源刺激，而对照动物除注射过程外未进行任何处理。在慢性实验的最后一次事件一天后，对照动物和应激动物接受生理盐水或吗啡（0.75或1.5毫克/千克，腹腔注射），并在90分钟内评估它们的运动能力。在另一项实验中，在最后一次应激源刺激24小时后，应激大鼠和对照大鼠接受生理盐水或两种较高剂量（行为抑制性）吗啡（5和10毫克/千克，腹腔注射）之一的激发试验。与对照大鼠相比，慢性应激大鼠在低剂量（1.5毫克/千克）吗啡注射后运动活动的增加明显更大。去甲丙咪嗪预处理可防止应激大鼠对吗啡的这种增强的运动反应。慢性可变应激处理并未改变对高剂量吗啡的镇静反应。这些数据支持以下观点，即慢性可变应激程序导致对阿片类刺激的兴奋作用产生敏化，并且抗抑郁药去甲丙咪嗪预处理可阻断这种敏化的发展。
