Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Italy.
Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Italy.
Int J Eat Disord. 2019 Nov;52(11):1251-1262. doi: 10.1002/eat.23157. Epub 2019 Aug 27.
Despite the growing knowledge on the functional relationship between an altered endocannabinoid (eCB) system and development of anorexia nervosa (AN), to date no studies have investigated the central eCB tone in the activity-based anorexia (ABA) model that reproduces key aspects of human AN.
We measured levels of two major eCBs, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), those of two eCB-related lipids, oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), and the cannabinoid type-1 receptor (CB1R) density in the brain of female ABA rats, focusing on areas involved in homeostatic and rewarding-related regulation of feeding behavior (i.e., prefrontal cortex, nucleus accumbens, caudato putamen, amygdala, hippocampus and hypothalamus). Analysis was carried out also at the end of recovery from the ABA condition.
At the end of the ABA induction phase, 2-AG was significantly decreased in ABA rats in different brain areas but not in the caudato putamen. No changes were detected in AEA levels in any region, whereas the levels of OEA and PEA were decreased exclusively in the hippocampus and hypothalamus. Furthermore, CB1R density was decreased in the dentate gyrus of hippocampus and in the lateral hypothalamus. After recovery, both 2-AG levels and CB1R density were partially normalized in some areas. In contrast, AEA levels became markedly reduced in all the analyzed areas.
These data demonstrate an altered brain eCB tone in ABA rats, further supporting the involvement of an impaired eCB system in AN pathophysiology that may contribute to the maintenance of some symptomatic aspects of the disease.
尽管人们对改变的内源性大麻素（eCB）系统与厌食症（AN）发展之间的功能关系有了更多的了解，但迄今为止，尚无研究调查可重现人类 AN 关键方面的活动性厌食（ABA）模型中的中枢 eCB 张力。
我们测量了两种主要 eCB，花生四烯酰乙醇胺（AEA）和 2-花生四烯酰甘油（2-AG），两种与 eCB 相关的脂质，油酰乙醇胺（OEA）和棕榈酰乙醇胺（PEA），以及大脑中女性 ABA 大鼠的大麻素 1 型受体（CB1R）密度，重点关注与摄食行为的稳态和奖励相关调节有关的区域（即前额叶皮层、伏隔核、尾壳核、杏仁核、海马体和下丘脑）。分析还在从 ABA 条件恢复结束时进行。
在 ABA 诱导阶段结束时，不同脑区的 2-AG 在 ABA 大鼠中明显降低，但尾壳核除外。在任何区域均未检测到 AEA 水平的变化，而 OEA 和 PEA 水平仅在海马体和下丘脑降低。此外，CB1R 密度在海马体的齿状回和外侧下丘脑中降低。恢复后，2-AG 水平和 CB1R 密度在一些区域部分恢复正常。相比之下，所有分析区域的 AEA 水平明显降低。
这些数据表明 ABA 大鼠的大脑 eCB 张力发生改变，进一步支持受损的 eCB 系统在 AN 病理生理学中的参与，这可能有助于维持疾病的某些症状方面。
