Giraudo S Q, Billington C J, Levine A S
Minnesota Obesity Center, VA Medical Center, Minneapolis, USA.
Brain Res. 1998 Jan 26;782(1-2):18-23. doi: 10.1016/s0006-8993(97)01140-2.
The paraventricular nucleus of the hypothalamus (PVN) and the central nucleus of the amygdala (CNA) are two forebrain structures which are important in regulation of ingestive behavior. DAMGO is one of the most reliable and potent mu-selective opioid ligands that increases feeding in both of these brain nuclei. Administration of naloxone, an opioid antagonist, into the CNA prior to DAMGO blocks DAMGO-induced increases in food intake. The effect of this drug combination on food intake has not been evaluated in the PVN. However, intra-PVN injection of naloxone decreases deprivation and NPY-induced feeding. It has been suggested that CNA may modulate activity of midbrain and caudal brainstem centers via the hypothalamus. Based on these data, we evaluated whether an opioid-opioid interaction is present between the CNA and PVN which might affect feeding behavior. To test this, rats were doubly cannulated with 1 cannula placed in the PVN and 1 cannula in the CNA, allowing for co-administration of the opioid agonist into the PVN and the opioid antagonist into the CNA, and vice versa. CNA DAMGO increased feeding more than two-fold as compared to the vehicle-injected rats. When doses of 10, 12.5 and 25 micrograms of naltrexone (NTX) were injected into the PVN, CNA DAMGO no longer increased food intake above control levels. In the reverse situation, PVN DAMGO also increased food intake above control levels. However, when NTX was administrated unilaterally into the CNA at a relatively high dose (25 micrograms) or bilaterally (12.5 micrograms), PVN DAMGO-induced feeding was not altered. This suggests that an opioid-opioid signaling pathway exists from the CNA to the PVN which influences feeding via mu opioid receptors, whereas such a pathway from the PVN to the CNA does not seem to exist.
下丘脑室旁核（PVN）和杏仁核中央核（CNA）是前脑结构中的两个，它们在调节摄食行为方面很重要。DAMGO是最可靠且强效的μ-选择性阿片样物质配体之一，可增加这两个脑核中的摄食量。在给予DAMGO之前，向CNA注射阿片样物质拮抗剂纳洛酮可阻断DAMGO诱导的食物摄入量增加。这种药物组合对食物摄入量的影响尚未在PVN中进行评估。然而，向PVN内注射纳洛酮可减少禁食和神经肽Y诱导的摄食。有人提出，CNA可能通过下丘脑调节中脑和延髓脑干中枢的活动。基于这些数据，我们评估了CNA和PVN之间是否存在可能影响摄食行为的阿片样物质-阿片样物质相互作用。为了验证这一点，将大鼠双侧插管，一根插管置于PVN，另一根置于CNA，以便将阿片样物质激动剂注入PVN，将阿片样物质拮抗剂注入CNA，反之亦然。与注射赋形剂的大鼠相比，CNA注射DAMGO使摄食量增加了两倍多。当向PVN注射10、12.5和25微克的纳曲酮（NTX）时，CNA注射DAMGO不再使食物摄入量增加到对照水平以上。在相反的情况下，PVN注射DAMGO也使食物摄入量增加到对照水平以上。然而，当以相对高剂量（25微克）单侧或双侧（12.5微克）向CNA注射NTX时，PVN注射DAMGO诱导的摄食没有改变。这表明存在一条从CNA到PVN的阿片样物质-阿片样物质信号通路，其通过μ阿片受体影响摄食，而从PVN到CNA的这样一条通路似乎不存在。
