Gosnell B A, Krahn D D
Department of Psychiatry, University of Wisconsin-Madison, Parkway Hospital 53719.
Pharmacol Biochem Behav. 1993 Apr;44(4):919-24. doi: 10.1016/0091-3057(93)90025-o.
Rats of the Lewis inbred strain have been shown to self-administer more morphine than rats of the inbred Fischer 344 (F344) strain. Because morphine reward and opioid-induced feeding may involve a common mechanism, we measured whether these strains also differ in their feeding response to morphine. In Experiment 1, rats were maintained on powdered rat chow and given SC injections of morphine sulfate (1, 3, and 10 mg/kg) and saline; all rats were tested with all doses. Food intake was measured 2, 4, and 6 h after injection. In Experiment 2, rats were given a choice of two diets: a fat/protein diet and a carbohydrate/protein diet. Feeding responses to morphine were measured in a manner identical to that in Experiment 1. In both experiments, the feeding response to morphine was greater in Lewis rats than in F344 rats. To determine whether these responses might be explained by differences in the levels of morphine achieved in the blood or brain, rats of each strain were given SC injections of morphine sulfate (3 mg/kg) and sacrificed either 30 min or 3 h after injection. Serum and brain morphine levels were determined by radioimmunoassay. Lewis rats had significantly less brain morphine than F344 rats at 30 min; they did not differ in morphine content at 3 h. Serum levels were similar at 30 min; at 3 h, F344 rats had slightly lower levels than Lewis rats. Thus, differences in tissue levels cannot readily explain the differences in feeding responses to morphine.(ABSTRACT TRUNCATED AT 250 WORDS)
研究表明,近交系Lewis大鼠比近交系Fischer 344(F344)大鼠能自我给药更多的吗啡。由于吗啡奖赏和阿片类药物诱导的进食可能涉及共同机制,我们测定了这些品系对吗啡的进食反应是否也存在差异。在实验1中,大鼠维持食用粉状大鼠饲料,并皮下注射硫酸吗啡(1、3和10mg/kg)及生理盐水;所有大鼠均接受所有剂量测试。在注射后2、4和6小时测量食物摄入量。在实验2中,大鼠可在两种饮食中选择:高脂肪/蛋白质饮食和高碳水化合物/蛋白质饮食。以与实验1相同的方式测量对吗啡的进食反应。在两个实验中,Lewis大鼠对吗啡的进食反应均大于F344大鼠。为了确定这些反应是否可能由血液或大脑中吗啡水平的差异所解释,给每个品系的大鼠皮下注射硫酸吗啡(3mg/kg),并在注射后30分钟或3小时处死。通过放射免疫测定法测定血清和大脑中的吗啡水平。在30分钟时,Lewis大鼠大脑中的吗啡含量显著低于F344大鼠;在3小时时,它们的吗啡含量没有差异。30分钟时血清水平相似;在3小时时,F344大鼠的水平略低于Lewis大鼠。因此,组织水平的差异不能轻易解释对吗啡进食反应的差异。(摘要截断于250字)