Chu Shu-Chen, Chen Pei-Ni, Ho Ying-Jui, Yu Ching-Han, Hsieh Yih-Shou, Kuo Dong-Yih
Department of Food Science, Central Taiwan University of Science and Technology, Taichung City 406, Taiwan, ROC.
Institute of Biochemistry and Biotechnology, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung City 40201, Taiwan, ROC.
Horm Behav. 2015 Jan;67:38-47. doi: 10.1016/j.yhbeh.2014.11.005. Epub 2014 Nov 20.
Amphetamine (AMPH)-induced appetite suppression has been attributed to its inhibition of neuropeptide Y (NPY)-containing neurons in the hypothalamus. This study examined whether hypothalamic cocaine- and amphetamine-regulated transcript (CART)-containing neurons and NPY Y1 receptor (Y1R) were involved in the action of AMPH. Rats were treated daily with AMPH for four days, and changes in feeding behavior and expression levels of NPY, CART, and POMC were assessed and compared. The results showed that both feeding behavior and NPY expression decreased during AMPH treatment, with the biggest reduction occurring on Day 2. By contrast, the expression of CART and melanocortin 3 receptor (MC3R), a member of the POMC neurotransmission, increased with the maximum response on Day 2, directly opposite to the NPY expression results. The intracerebroventricular infusion of NPY antisense or Y1R inhibitor both modulated AMPH-induced anorexia and the expression levels of MC3R and CART. The results suggest that in the hypothalamus both POMC- and CART-containing neurons participate in regulating NPY-mediated appetite control during AMPH treatment. These results may advance the knowledge of molecular mechanism of anorectic drugs.
苯丙胺（AMPH）引起的食欲抑制归因于其对下丘脑含神经肽Y（NPY）神经元的抑制作用。本研究探讨了下丘脑含可卡因和苯丙胺调节转录物（CART）的神经元以及NPY Y1受体（Y1R）是否参与AMPH的作用。大鼠连续四天每日接受AMPH治疗，并评估和比较进食行为以及NPY、CART和阿黑皮素原（POMC）表达水平的变化。结果显示，在AMPH治疗期间，进食行为和NPY表达均下降，最大降幅出现在第2天。相比之下，CART和POMC神经传递成员黑皮质素3受体（MC3R）的表达增加，在第2天达到最大反应，与NPY表达结果正好相反。脑室内注入NPY反义寡核苷酸或Y1R抑制剂均能调节AMPH诱导的厌食以及MC3R和CART的表达水平。结果表明，在下丘脑中，含POMC和CART的神经元在AMPH治疗期间均参与调节NPY介导的食欲控制。这些结果可能会推动对厌食药物分子机制的认识。
