Taveira da Silva A M, Souza J D, Quest J A, Pagani F D, Moerschbaecher J M, Buller A, Hamosh P, Gillis R A
J Clin Invest. 1983 Oct;72(4):1209-17. doi: 10.1172/JCI111076.
The purpose of our study was to identify central nervous system sites involved in the respiratory depressant effect of drugs that stimulate opioid receptors. Diacetylmorphine (heroin) was administered into several cerebroventricular regions of chloralose-anesthetized cats, while monitoring pulmonary ventilation with a Fleisch pneumotachograph. Administration of heroin (17, 50, 150, and 450 micrograms) into the forebrain ventricles, which was restricted to these ventricles, resulted in no significant respiratory effects. In contrast, administration of heroin into either the fourth ventricle or the cisterna magna resulted in a significant (P less than 0.05) decrease in respiratory minute volume (VE). In the fourth ventricle this was because of a decrease in frequency (f) and in the cisterna magna, to a decrease in tidal volume (VT). Intravenous administration of heroin in the same dose-range produced a decrease in VE, which was primarily due to a decrease in f. Bilateral application of heroin (70 micrograms/side) to each of three ventral medullary surface sites (Mitchell's, Schlaefke's, and Loeschcke's areas) known to influence respiration elicited a decrease in VE only at Mitchell's area. This decrease was due to decreases in f and VT. The role of this site in the action of intravenously administered heroin was tested by topical application of naloxone to this area in animals with respiratory depression evoked by intravenous heroin. Bilateral application of naloxone (15 micrograms/side) to Mitchell's area restored breathing to normal. These results lead us to suggest that the site of heroin-induced respiratory depression is a specific area (Mitchell's area) on the ventral surface of the medulla.
我们研究的目的是确定参与刺激阿片受体的药物呼吸抑制作用的中枢神经系统部位。将二乙酰吗啡（海洛因）注入用氯醛糖麻醉的猫的几个脑室区域，同时用Fleisch呼吸速度描记器监测肺通气。将海洛因（17、50、150和450微克）注入仅限于前脑脑室，未产生明显的呼吸效应。相比之下，将海洛因注入第四脑室或小脑延髓池会导致呼吸分钟量（VE）显著（P<0.05）下降。在第四脑室，这是由于频率（f）降低，而在小脑延髓池，则是由于潮气量（VT）降低。静脉注射相同剂量范围的海洛因会导致VE下降，这主要是由于f降低。将海洛因（70微克/侧）双侧应用于已知影响呼吸的三个延髓腹侧表面部位（米切尔区、施莱夫克区和勒施克区），仅在米切尔区引起VE下降。这种下降是由于f和VT降低。通过在静脉注射海洛因引起呼吸抑制的动物中，将纳洛酮局部应用于该区域，测试了该部位在静脉注射海洛因作用中的作用。将纳洛酮（15微克/侧）双侧应用于米切尔区可使呼吸恢复正常。这些结果使我们认为，海洛因诱导呼吸抑制的部位是延髓腹侧表面的一个特定区域（米切尔区）。
