Soria-Gómez E, Matias I, Rueda-Orozco P E, Cisneros M, Petrosino S, Navarro L, Di Marzo V, Prospéro-García O
Grupo de Neurociencias, Depto. de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico DF 04510, Mexico.
Br J Pharmacol. 2007 Aug;151(7):1109-16. doi: 10.1038/sj.bjp.0707313. Epub 2007 Jun 4.
Evidence indicates that the endocannabinoid, 2-arachidonoylglycerol (2-AG), increases food intake when injected into the nucleus accumbens shell (NAcS), thereby potentially activating hypothalamic nuclei involved in food intake regulation. We aimed to evaluate potential orexigenic effects of the endocannabinoid anandamide and of AA5HT, a fatty acid amide hydrolase (FAAH) inhibitor, and OMDM-1, an inhibitor of anandamide uptake, injected in the NAcS, as well as the effect of these treatments on activation of hypothalamic nuclei.
Drugs were given into the NAcS of rats and food intake quantified during the next 4 h. In other groups, after the same treatments the brains were processed for c-Fos immunohistochemistry with focus on hypothalamic nuclei. Additional groups were used to quantify endocannabinoid levels in the nucleus accumbens and the hypothalamus after AA5HT and OMDM-1 intra-NAcS injections.
Our results indicate that the above treatments stimulate food intake during 4 h post-injection. They also increase c-Fos immunoreactivity in hypothalamic nuclei. The CB(1) antagonist, AM251, blocked these effects. Finally, we found elevated levels of 2-AG, but not anandamide, after intra-NAcS injections of AA5HT.
These data support the involvement of the endocannabinoid system in feeding behavior at the level of the NAcS and hypothalamus. In addition, this is the first experimental demonstration that the pharmacological inhibition of endocannabinoid inactivation in the NAcS stimulates food intake, suggesting that the endocannabinoid degrading proteins can be a target for treating eating disorders.
有证据表明，内源性大麻素2-花生四烯酸甘油酯（2-AG）注入伏隔核壳（NAcS）时会增加食物摄入量，从而可能激活参与食物摄入调节的下丘脑核团。我们旨在评估内源性大麻素花生四烯酸乙醇胺以及脂肪酸酰胺水解酶（FAAH）抑制剂AA5HT和花生四烯酸乙醇胺摄取抑制剂OMDM-1注入NAcS后的潜在促食欲作用，以及这些处理对下丘脑核团激活的影响。
将药物注入大鼠的NAcS，并在接下来的4小时内对食物摄入量进行量化。在其他组中，经过相同处理后，对大脑进行c-Fos免疫组织化学处理，重点关注下丘脑核团。另外的组用于量化在NAcS内注射AA5HT和OMDM-1后伏隔核和下丘脑中内源性大麻素的水平。
我们的结果表明，上述处理在注射后4小时内刺激食物摄入。它们还增加了下丘脑核团中的c-Fos免疫反应性。CB(1)拮抗剂AM251阻断了这些作用。最后，我们发现NAcS内注射AA5HT后2-AG水平升高，但花生四烯酸乙醇胺水平未升高。
这些数据支持内源性大麻素系统在NAcS和下丘脑水平参与进食行为。此外，这是首次实验证明在NAcS中对内源性大麻素失活的药理学抑制会刺激食物摄入，表明内源性大麻素降解蛋白可能是治疗饮食失调的靶点。
