Beckman Tiffany R, Shi Qiuying, Levine Allen S, Billington Charles J
Department of Medicine, University of Minnesota, Minneapolis, MN 55455, United States.
Physiol Behav. 2009 Mar 23;96(4-5):568-73. doi: 10.1016/j.physbeh.2008.12.007. Epub 2008 Dec 24.
We wanted to assess the possibility that opioid activity in the central amygdala (CeA) could modulate the feeding inhibition of melanocortin stimulation of the paraventricular hypothalamus (PVN). The melanocortin system is important in both the acute regulation of satiety and feeding behavior and in the integration of long-term appetite signals. Melanotan II (MTII) is a synthetic MC3R and MC4R agonist which reduces food intake when given intracerebroventricularly (ICV) and into the PVN. Tyr-D-Ala-Gly-(me) Phe-Gly-ol (DAMGO), a micro-opioid receptor agonist, increases food intake, while opioid antagonists, like naltrexone (NTX), inhibit food intake after injection into many brain sites involved in appetite regulation, including the CeA. In food-deprived male Sprague-Dawley rats, co-injected intra-PVN MTII partially blocked the orexigenic effect of co-injected intra-CeA DAMGO. Intra-CeA NTX co-injected with intra-PVN MTII reduced food intake significantly more than either alone. NTX administered intra-CeA reduced c-Fos-immunoreactivity (IR) in nucleus accumbens neurons significantly compared to the intra-PVN MTII treated animals, animals co-injected intra-PVN with MTII and intra-CeA with NTX animals, and control animals. Intra-PVN MTII induced c-Fos-IR in significantly more PVN neurons than observed in control animals. Intra-CeA NTX co-injected with intra-PVN MTII induced c-Fos-IR significantly in PVN neurons relative to control and intra-CeA NTX animals. Such data support the significance of opioid action within the CeA as a modulator of the feeding regulation action of melanocortins within the PVN, occurring within the context of a larger appetitive network.
我们想要评估中央杏仁核（CeA）中的阿片类活性是否能够调节室旁下丘脑（PVN）中黑皮质素刺激所产生的进食抑制作用。黑皮质素系统在饱腹感和进食行为的急性调节以及长期食欲信号的整合过程中均发挥着重要作用。黑素皮质素II（MTII）是一种合成的MC3R和MC4R激动剂，当脑室内（ICV）给药或注入PVN时可减少食物摄入量。酪酪肽（DAMGO），一种微阿片受体激动剂，可增加食物摄入量，而阿片类拮抗剂，如纳曲酮（NTX），在注入包括CeA在内的许多参与食欲调节的脑区后可抑制食物摄入。在食物剥夺的雄性Sprague-Dawley大鼠中，PVN内共同注射MTII可部分阻断CeA内共同注射DAMGO所产生的促食欲作用。与单独注射相比，CeA内共同注射NTX与PVN内共同注射MTII可显著减少更多食物摄入量。与PVN内注射MTII处理的动物、PVN内与MTII共同注射且CeA内与NTX共同注射的动物以及对照动物相比，CeA内注射NTX可显著降低伏隔核神经元中的c-Fos免疫反应性（IR）。PVN内注射MTII诱导产生c-Fos-IR的PVN神经元数量显著多于对照动物。与对照动物和CeA内注射NTX的动物相比，CeA内共同注射NTX与PVN内共同注射MTII可在PVN神经元中显著诱导产生c-Fos-IR。这些数据支持了CeA内阿片类作用作为PVN内黑皮质素进食调节作用的调节剂的重要性，这一过程发生在更大的食欲网络背景下。
