Laschka E, Herz A
Psychopharmacology (Berl). 1977 Jun 6;53(1):33-7. doi: 10.1007/BF00426691.
Morphine withdrawal was precipitated by injection of 3H-naloxone into restricted parts of the ventricular system of rats made tolerant to and dependent on morphine by repeated pellet implantation. The spread of the drug was evaluated by autoradiography and compared with the withdrawal signs precipitated in the same experiment. When the antagonist could spread into the tissue surrounding the 4th ventricle and the caudal parts of the aqueduct (penetration depth about 1.5 mm), a strong withdrawal syndrome was displayed. In contrast, only weak or no withdrawal signs were observed when the spread of naloxone was restricted to the surroundings of the lateral ventricles, the 3rd ventricle, and the rostromedial parts of the aqueduct. The same was true when the spread of the antagonist was limited to the ventral surface of the brain stem. It is concluded that structures located in the anterior part of the fossa Rhomboidea, and possibly also in the caudal part of the periaqueductal grey matter, are sites for the development of physical dependence on morphine giving rise to the withdrawal signs studied in these experiments.
通过向经反复植入药粒而对吗啡产生耐受性和依赖性的大鼠脑室系统的特定部位注射3H-纳洛酮来引发吗啡戒断反应。通过放射自显影评估药物的扩散情况，并与同一实验中引发的戒断症状进行比较。当拮抗剂能够扩散到第四脑室周围组织和导水管尾部（穿透深度约1.5毫米）时，会出现强烈的戒断综合征。相比之下，当纳洛酮的扩散仅限于侧脑室周围、第三脑室以及导水管的嘴内侧部分时，仅观察到微弱的戒断症状或无戒断症状。当拮抗剂的扩散仅限于脑干腹侧表面时，情况也是如此。得出的结论是，位于菱形窝前部以及可能还在导水管周围灰质尾部的结构，是产生对吗啡身体依赖性并引发这些实验中所研究的戒断症状的部位。
