Zhang M, Gosnell B A, Kelley A E
Department of Psychology, University of Wisconsin-Madison, USA.
J Pharmacol Exp Ther. 1998 May;285(2):908-14.
The present study was designed to further investigate the nature of feeding induced by opioid stimulation of the nucleus accumbens through an examination of the effects of intra-accumbens (ACB) opioids on macronutrient selection. In 3-hr tests of free-feeding (satiated) rats, intra-ACB administration of the mu receptor agonist D-Ala2,N,Me-Phe4, Gly-ol5-enkephalin (DAMGO; 0, 0.025, 0.25 and 2.5 micrograms bilaterally) markedly enhanced the intake of fat or carbohydrate when the diets were presented individually (although the effect on fat intake was much greater in magnitude). Intra-ACB injections of DAMGO, however, produced potent preferential stimulatory effects on fat ingestion with no effect on carbohydrate ingestion when both fat and carbohydrate diets were present simultaneously. Moreover, this selective stimulation of fat intake was independent of base-line diet preference and could be blocked by systemic injection of naltrexone (5 mg/kg). We also examined the effect of 24-hr food deprivation on the pattern of macronutrient intake in rats with access to both carbohydrate and fat. In contrast to the DAMGO-induced selective enhancement of fat intake, food deprivation significantly increased the intake of both diets to the same extent; however, in this case, only the stimulated fat intake was blocked by systemic naltrexone. Intra-ACB administration of DAMGO in hungry rats produced an effect similar to that observed in free-feeding rats; preference was strongly shifted to fat intake. Similarly, the opioid antagonist naltrexone (20 micrograms) infused directly into ACB preferentially decreased fat intake in hungry rats. These findings suggest that endogenous opioids within the ventral striatum may participate in the mechanisms governing preferences for highly palatable foods, especially those rich in fat.
本研究旨在通过检查伏隔核内阿片类药物对常量营养素选择的影响，进一步探究伏隔核阿片类药物刺激诱导的进食本质。在对饱腹大鼠进行的3小时自由进食试验中，双侧伏隔核内注射μ受体激动剂D-Ala2，N，Me-Phe4，Gly-ol5-脑啡肽（DAMGO；0、0.025、0.25和2.5微克），当单独提供饮食时，显著增加了脂肪或碳水化合物的摄入量（尽管对脂肪摄入的影响在程度上要大得多）。然而，当脂肪和碳水化合物饮食同时存在时，伏隔核内注射DAMGO对脂肪摄入产生了强烈的优先刺激作用，而对碳水化合物摄入没有影响。此外，这种对脂肪摄入的选择性刺激与基线饮食偏好无关，并且可以被全身注射纳曲酮（5毫克/千克）阻断。我们还研究了24小时食物剥夺对可同时获取碳水化合物和脂肪的大鼠常量营养素摄入模式的影响。与DAMGO诱导的脂肪摄入选择性增强相反，食物剥夺显著增加了两种饮食的摄入量，且程度相同；然而，在这种情况下，只有受刺激的脂肪摄入被全身纳曲酮阻断。在饥饿大鼠中伏隔核内注射DAMGO产生的效果与在自由进食大鼠中观察到的效果相似；偏好强烈转向脂肪摄入。同样，直接注入伏隔核的阿片类拮抗剂纳曲酮（20微克）优先降低了饥饿大鼠的脂肪摄入量。这些发现表明，腹侧纹状体内的内源性阿片类物质可能参与了控制对高度可口食物，尤其是富含脂肪食物偏好的机制。
