Bocarsly M E, Avena N M
Department of Psychology, Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA.
Department of Psychology, Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA; Department of Psychiatry, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
Neuroscience. 2013 Sep 17;248:61-6. doi: 10.1016/j.neuroscience.2013.05.046. Epub 2013 Jun 6.
A high-fat diet (HFD) can increase hypothalamic galanin (GAL). GAL has recently been shown to inhibit opiate reward, which in turn, decreases cAMP response element-binding protein (CREB) in the nucleus accumbens (NAc). We hypothesized that injection of GAL into the paraventricular nucleus (PVN), or consumption of a HFD, would be associated with a decrease in NAc CREB. In Exp. 1, GAL in the PVN of naïve rats decreased phosphorylated-CREB (pCREB) which is the activated form of CREB, in the NAc compared to saline-injected controls. In Exp. 2, rats fed ad libitum HFD for 4 weeks had reduced NAc pCREB levels compared to rats with sporadic tastes of the HFD. Body weight, serum triglyceride and leptin levels were also raised in the chronic HFD-fed rats. These data suggest that PVN GAL or chronic intake of a HFD can decrease NAc pCREB. The implications of these findings may help to explain the lack of opiate-like withdrawal that has been reported in response to overeating a HFD, thereby providing a potential mechanism underlying behavioral differences seen with addiction-like overconsumption of different types of palatable foods.
高脂饮食（HFD）会增加下丘脑甘丙肽（GAL）。最近研究表明，GAL可抑制阿片类奖赏，进而降低伏隔核（NAc）中的环磷酸腺苷反应元件结合蛋白（CREB）。我们推测，向室旁核（PVN）注射GAL或食用HFD会导致NAc中CREB减少。在实验1中，与注射生理盐水的对照组相比，向未接触过HFD的大鼠PVN中注射GAL后，NAc中磷酸化CREB（pCREB，即CREB的活化形式）减少。在实验2中，与偶尔食用HFD的大鼠相比，自由进食HFD 4周的大鼠NAc中pCREB水平降低。长期喂食HFD的大鼠体重、血清甘油三酯和瘦素水平也有所升高。这些数据表明，PVN中的GAL或长期摄入HFD可降低NAc中的pCREB。这些发现的意义可能有助于解释因过量食用HFD而未出现类似阿片类戒断反应的现象，从而为不同类型美味食物成瘾性过度消费所表现出的行为差异提供潜在机制。
