Akunne H C, Soliman K F
College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee 32307.
Psychopharmacology (Berl). 1988;96(1):1-6. doi: 10.1007/BF02431525.
Male Sprague-Dawley rats maintained under controlled lighting and temperature conditions were used in this experiment. Morphine dependency was induced by giving increasing doses of morphine by intraperitoneal injection (IP group) or by the ingestion of morphine through drinking water (PO group). Animals were injected with 10, 20, 30 and 50 mg/kg morphine sulfate at days 1, 2, 3 and 4, respectively. Another group of animals received increasing concentrations of morphine through drinking water from 0.1, 0.2, 0.3 to 0.4 mg/ml at 48 h intervals. Morphine dependent animals were given naloxone by the intraperitoneal route to precipitate withdrawal. Glucose (3 g/kg or 10 g/kg) was given 10 min prior to the administration of naloxone to the respective groups. Another two groups of animals were made diabetic by the administration of streptozotocin. In one group, animals received increasing concentrations of 10, 20, 30 and 50 mg/kg morphine sulfate by the IP route at days 1, 2, 3 and 4, while the other group was not treated with morphine but was assessed for withdrawal signs to serve as the control. Withdrawal signs were assessed by observing the presence of diarrhea, tremor, piloerection, hunchbacked posture, teeth chattering, salivation, erection, restless activity, territorial exploring, irritability to handling, vocalization and jumping. Results obtained indicate that glucose administration at 10 g/kg abolished most of the withdrawal signs, and we were unable to induce the same degree of morphine dependency in diabetic animals as compared to the non-diabetic groups. It was concluded from this study that hyperglycemia could suppress morphine withdrawal signs.
本实验使用在光照和温度条件受控的环境下饲养的雄性Sprague-Dawley大鼠。通过腹腔注射递增剂量的吗啡（腹腔注射组）或通过饮水摄入吗啡（口服组）诱导吗啡依赖。分别在第1、2、3和4天给动物注射10、20、30和50mg/kg硫酸吗啡。另一组动物每隔48小时通过饮水摄入浓度从0.1、0.2、0.3至0.4mg/ml递增的吗啡。对吗啡依赖的动物腹腔注射纳洛酮以引发戒断反应。在给各相应组注射纳洛酮前10分钟给予葡萄糖（3g/kg或10g/kg）。另外两组动物通过注射链脲佐菌素制成糖尿病模型。一组动物在第1、2、3和4天通过腹腔注射途径接受浓度递增的10、20、30和50mg/kg硫酸吗啡，而另一组未用吗啡处理但评估其戒断体征作为对照。通过观察是否存在腹泻、震颤、竖毛、驼背姿势、磨牙、流涎、勃起、活动不安、领地探索、对处理的易激惹性、鸣叫和跳跃来评估戒断体征。获得的结果表明，给予10g/kg葡萄糖可消除大部分戒断体征，并且与非糖尿病组相比，我们无法在糖尿病动物中诱导出相同程度的吗啡依赖。从本研究得出结论，高血糖可抑制吗啡戒断体征。
