Reddy P L, Thorat S N, Bhargava H N
Department of Pharmacodynamics, University of Illinois, Chicago 60612.
Brain Res. 1993 Apr 2;607(1-2):293-300. doi: 10.1016/0006-8993(93)91519-x.
The effect of morphine tolerance-dependence and abstinence on the characteristics of dopamine D2 receptors in brain regions and spinal cord was determined in the rat. Male Sprague-Dawley rats were implanted s.c. under light ether anesthesia with 6 morphine pellets for a 7-day period, each containing 75 mg of morphine free base. Rats implanted with placebo pellets served as controls. This procedure resulted in the development of tolerance to morphine as evidenced by decreased analgesic response to a challenge dose of morphine. Similarly, the development of physical dependence was evidenced by a decrease in body weight and colonic temperature after morphine pellet removal (withdrawal). The binding characteristics (Bmax and Kd values) of [3H]spiroperidol to dopamine D2 receptors were determined in the tissues of morphine-tolerant and morphine-abstinent rats. In the tolerant rats, the pellets were left intact at the time of sacrificing, whereas, in the abstinent rats the pellets were removed 18 h prior to sacrificing. The binding of [3H]spiroperidol was determined in membranes prepared from brain regions (hypothalamus, hippocampus, cortex, pons and medulla, midbrain, corpus striatum and amygdala) and spinal cord of rats from various treatment groups. [3H]Spiroperidol bound to brain regions and spinal cord at a single high affinity site. The Bmax or the Kd values in brain regions and spinal cord of morphine-tolerant and -abstinent rats did not differ from their respective placebo controls. The behavioral responses to a selective dopamine D2 receptor agonist, 2-bromo-alpha-ergocryptine were also determine in the morphine-abstinent rats.(ABSTRACT TRUNCATED AT 250 WORDS)
在大鼠中确定了吗啡耐受-依赖和戒断对脑区和脊髓中多巴胺D2受体特性的影响。雄性Sprague-Dawley大鼠在轻度乙醚麻醉下皮下植入6个吗啡丸粒，持续7天，每个丸粒含75mg吗啡游离碱。植入安慰剂丸粒的大鼠作为对照。该程序导致对吗啡产生耐受性，这可通过对挑战剂量吗啡的镇痛反应降低来证明。同样，吗啡丸粒去除后（戒断）体重和结肠温度下降证明了身体依赖性的发展。在吗啡耐受和吗啡戒断大鼠的组织中测定了[3H]螺哌啶醇与多巴胺D2受体的结合特性（Bmax和Kd值）。在耐受大鼠中，处死时丸粒保持完整，而在戒断大鼠中，处死前18小时取出丸粒。在来自不同治疗组的大鼠的脑区（下丘脑、海马、皮层、脑桥和延髓、中脑、纹状体和杏仁核）和脊髓制备的膜中测定[3H]螺哌啶醇的结合。[3H]螺哌啶醇在脑区和脊髓的一个单一高亲和力位点结合。吗啡耐受和戒断大鼠脑区和脊髓中的Bmax或Kd值与其各自的安慰剂对照无差异。还在吗啡戒断大鼠中测定了对选择性多巴胺D2受体激动剂2-溴-α-麦角隐亭的行为反应。（摘要截短于250字）
