Sites of action of morphine involved in the development of physical dependence in rats. II. Morphine withdrawal precipitated by application of morphine antagonists into restricted parts of the ventricular system and by microinjection into various brain areas.

E Laschka, H Teschemacher, P Mehraein, A Herz
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引用次数: 26

Abstract

Morphine withdrawal was precipitated by injection of various morphine antagonists into restricted parts of the ventricular system or by microinjection of levallorphan into specific brain areas of rats made dependent on morphine by repeated pellet implantation. When the antagonists could spread only within the lateral ventricles and the 3rd ventricle, a weak withdrawal syndrome was induced; by antagonist administration into the restricted 4th ventricle, however, strong withdrawal signs like jumping were elicited even at small dosages. In microinjection experiments, structures in the midbrain and the lower brain stem proved to be the most sensitive to antagonist action. Although microinjections into thalamic nuclei also had some effect, it could not be excluded that the effects were due to uncontrolled spreading of the drug. This became especially clear from experiments with tritium-labeled levallorphan. It is concluded that brain structures located in the anterior parts of the floor of the 4th ventricle and/or caudal parts of the periaqueductal gray matter are important sites of action for the development of physical dependence on morphine.

吗啡在大鼠身体依赖发展中的作用部位。2吗啡拮抗剂应用于脑室系统的受限部位和显微注射到脑的各个区域引起吗啡戒断。
吗啡戒断可通过向心室系统受限部位注射各种吗啡拮抗剂或向反复植入吗啡依赖小丸的大鼠的特定脑区微量注射左旋左旋吗啡来实现。当拮抗剂仅能在侧脑室和第三脑室内扩散时,诱发弱戒断综合征;然而,通过拮抗剂进入受限的第四心室,即使在小剂量下也会引起强烈的戒断症状,如跳跃。在显微注射实验中,中脑和下脑干的结构被证明对拮抗剂作用最敏感。虽然对丘脑核进行显微注射也有一定效果,但不能排除这种效果是由于药物不受控制的扩散造成的。这一点在用氚标记的水平孤儿进行的实验中变得尤为明显。由此可见,位于第四脑室底前部和/或导水管周围灰质尾部的脑结构是吗啡物理依赖发展的重要作用部位。
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