Ardianto C, Yonemochi N, Yamamoto S, Yang L, Takenoya F, Shioda S, Nagase H, Ikeda H, Kamei J
Department of Pathophysiology and Therapeutics, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
Department of Physiology and Molecular Sciences, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
Neuroscience. 2016 Apr 21;320:183-93. doi: 10.1016/j.neuroscience.2016.02.002. Epub 2016 Feb 6.
The hypothalamus controls feeding behavior. Since central opioid systems may regulate feeding behavior, we examined the role of μ-, δ- and κ-opioid receptors in the lateral hypothalamus (LH), the hunger center, in feeding behavior of mice. Non-selective (naloxone; 3 mg/kg, s.c.) and selective μ- (β-funaltrexamine, β-FNA; 10 mg/kg, s.c.), δ- (naltrindole; 3 mg/kg, s.c.) and κ- (norbinaltorphimine, norBNI; 20 mg/kg, s.c.) opioid receptor antagonists significantly decreased food intake in food-deprived mice. The injection of naloxone (20 μg/side) into the LH significantly decreased food intake whereas the injection of naloxone (20 μg/side) outside of the LH did not affect food intake. The injection of β-FNA (2 μg/side), naltrindole (1 μg/side) or norBNI (2 μg/side) into the LH significantly decreased food intake. Furthermore, all these antagonists significantly decreased the mRNA level of preproorexin, but not those of other hypothalamic neuropeptides. In addition, the injection of the GABAA receptor agonist muscimol (5 μg/side) into the LH significantly decreased food intake, and this effect was abolished by the GABAA receptor antagonist bicuculline (50 μg/side). Muscimol (1mg/kg, i.p.) decreased the mRNA level of preproorexin in the hypothalamus. Naloxone (3mg/kg, s.c.) significantly increased the GABA level in the LH and both bicuculline and the GABA release inhibitor 3-mercaptopropionic acid (3-MP, 5 μg/side) attenuated the inhibitory effect of naloxone on feeding behavior. 3-MP also attenuated the effects of β-FNA and norBNI, but not that of naltrindole. These results show that opioid systems in the LH regulate feeding behavior through orexin neurons. Moreover, μ- and κ-, but not δ-, opioid receptor antagonists inhibit feeding behavior by activating GABA neurons in the LH.
下丘脑控制进食行为。由于中枢阿片系统可能调节进食行为，我们研究了μ-、δ-和κ-阿片受体在饥饿中枢外侧下丘脑（LH）的小鼠进食行为中的作用。非选择性（纳洛酮；3毫克/千克，皮下注射）和选择性μ-（β-氟纳曲酮，β-FNA；10毫克/千克，皮下注射）、δ-（纳曲吲哚；3毫克/千克，皮下注射）和κ-（去甲二氢吗啡酮，norBNI；20毫克/千克，皮下注射）阿片受体拮抗剂显著降低了饥饿小鼠的食物摄入量。向LH内注射纳洛酮（20微克/侧）显著降低了食物摄入量，而在LH外注射纳洛酮（20微克/侧）则不影响食物摄入量。向LH内注射β-FNA（2微克/侧）、纳曲吲哚（1微克/侧）或norBNI（2微克/侧）显著降低了食物摄入量。此外，所有这些拮抗剂均显著降低了前阿黑皮素原的mRNA水平，但未降低其他下丘脑神经肽的mRNA水平。此外，向LH内注射GABAA受体激动剂蝇蕈醇（5微克/侧）显著降低了食物摄入量，而GABAA受体拮抗剂荷包牡丹碱（50微克/侧）消除了这种作用。蝇蕈醇（1毫克/千克，腹腔注射）降低了下丘脑中前阿黑皮素原的mRNA水平。纳洛酮（3毫克/千克，皮下注射）显著提高了LH中的GABA水平，荷包牡丹碱和GABA释放抑制剂3-巯基丙酸（3-MP，5微克/侧）均减弱了纳洛酮对进食行为的抑制作用。3-MP也减弱了β-FNA和norBNI的作用，但未减弱纳曲吲哚的作用。这些结果表明LH中的阿片系统通过食欲素神经元调节进食行为。此外，μ-和κ-阿片受体拮抗剂而非δ-阿片受体拮抗剂通过激活LH中的GABA神经元来抑制进食行为。
