Endocannabinoid levels in rat limbic forebrain and hypothalamus in relation to fasting, feeding and satiation: stimulation of eating by 2-arachidonoyl glycerol
Endocannabinoid levels in rat limbic forebrain and hypothalamus in relation to fasting, feeding and satiation: stimulation of eating by 2-arachidonoyl glycerol
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DOI：
10.1038/sj.bjp.0704767
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发表时间：
2002-06-01
影响因子：
7.3
通讯作者：
Di Marzo, V
中科院分区：
文献类型：
--
作者：
Kirkham, TC;Williams, CM;Di Marzo, V
1类内源性carinabinoids与食欲和体重调节有关。在啮齿类动物中，大麻素通过作用于中枢CB 1受体来刺激进食，而下丘脑内源性大麻素可能受瘦素的负控制。然而，大脑内源性大麻素水平的变化与喂养或营养状况的变化直接相关，尚未研究。2我们测量了禁食期间、喂食可口食物期间或饱食后大鼠喂养相关脑区的花生四烯酸和2-花生四烯酸甘油（2-AG）水平。内源性大麻素水平进行了比较，在大鼠喂养自由，在他们的日常周期的一个点时，猫的动机是缺席。禁食增加了边缘前脑中大麻素和2-AG的水平，并在较小程度上增加了下丘脑中2-AG的水平。相比之下，下丘脑2-AG随着动物进食而下降。在饱食大鼠中未检测到变化，小脑中的内源性大麻素水平，不直接参与食物摄入控制的控制区域，不受任何操作的影响。3由于2-AG对进食期间的变化最敏感，并且在先前的研究中对瘦素调节最敏感，我们检查了2-AG注射到丘脑核壳时的行为效应，与进食动机密切相关的边缘前脑区域。2-AG有效地和剂量依赖性地刺激摄食。CBI受体拮抗剂SR 141716减弱了这种作用。4这些发现提供了第一个直接证据，证明在禁食和进食期间，内源性大麻素，特别是2-AG的脑水平发生了变化。这些作用的性质支持内源性大麻素在控制食欲动机中的作用。
1 Endocarinabinoids are implicated in appetite and body weight regulation. In rodents, anandamide stimulates eating by actions at central CB1 receptors, and hypothalamic endocannabinoids may be under the negative control of leptin. However, changes to brain endocannabinoid levels in direct relation to feeding or changing nutritional status have not been investigated.2 We measured anandamide and 2-arachidonoyl glycerol (2-AG) levels in feeding-associated brain regions of rats, during fasting, feeding of a palatable food, or after satiation. Endocannabinoid levels were compared to those in rats fed ad libitum, at a point in their daily cycle when motivation to cat was absent. Fasting increased levels of anandamide and 2-AG in the limbic forebrain and, to a lesser extent, of 2-AG in the hypothalamus. By contrast, hypothalamic 2-AG declined as animals ate. No changes were detected in satiated rats, Endocannabinoid levels in the cerebellum, a control region not directly involved in the control of food intake, were unaffected by any manipulation.3 As 2-AG was most sensitive to variation during feeding, and to leptin regulation in a previous study, we examined the behavioural effects of 2-AG when injected into the nucleus accumbens shell, a limbic forebrain area strongly linked to eating motivation. 2-AG potently, and dose-dependently, stimulated feeding. This effect was attenuated by the CBI receptor antagonist SR141716.4 These findings provide the first direct evidence of altered brain levels of endocannabinoids, and of 2-AG in particular, during fasting and feeding. The nature of these effects supports a role for endocannabinoids in the control of appetitive motivation.