Schneider Eve R, Rada Pedro, Darby Ryan D, Leibowitz Sarah F, Hoebel Bartley G
Department of Psychology, Princeton University, Princeton, New Jersey 08544, USA.
Alcohol Clin Exp Res. 2007 Nov;31(11):1858-65. doi: 10.1111/j.1530-0277.2007.00510.x. Epub 2007 Sep 11.
The question is which hypothalamic systems for food intake might play a role in ethanol intake and contribute to alcohol abuse. The peptide orexin was found to exhibit similar properties to galanin in its relation to dietary fat and may therefore be similar to galanin in having a stimulatory effect on alcohol intake.
Rats were trained to drink 10% ethanol, implanted with brain cannulas, and then injected in the paraventricular nucleus (PVN), lateral hypothalamus (LH), or nucleus accumbens (NAc) with galanin, orexin-A, and for comparison, ghrelin. Ethanol, food, and water intake were measured at 1, 2, and 4 hours postinjection.
In the PVN, both orexin and galanin significantly increased ethanol intake, whereas ghrelin increased food intake. In the LH, orexin again induced ethanol intake, while ghrelin increased eating. In the NAc, orexin failed to influence ethanol intake but did stimulate food intake.
In ethanol-drinking rats, injection of orexin or galanin into the appropriate locus in the hypothalamus induced significant ethanol intake instead of food intake. Ghrelin, as a positive control, failed to influence ethanol intake at the same hypothalamic sites. In the NAc, as an anatomical control, orexin augmented eating but not ethanol intake. Thus orexin and galanin in the hypothalamus selectively stimulated ethanol intake at sites where other studies have shown that both ethanol and fat increase expression of the endogenous peptides. Thus, a neural circuit that evolved with the capability to augment food intake is apparently co-opted by ethanol and may serve as a potential positive feedback circuit for alcohol abuse.
问题在于哪些下丘脑食物摄入系统可能在乙醇摄入中发挥作用并导致酒精滥用。人们发现肽类食欲素在与膳食脂肪的关系上表现出与甘丙肽相似的特性，因此在对酒精摄入的刺激作用方面可能与甘丙肽相似。
训练大鼠饮用10%的乙醇，植入脑套管，然后在室旁核（PVN）、下丘脑外侧区（LH）或伏隔核（NAc）注射甘丙肽、食欲素A，作为对照，还注射了胃饥饿素。在注射后1、2和4小时测量乙醇、食物和水的摄入量。
在PVN，食欲素和甘丙肽均显著增加乙醇摄入量，而胃饥饿素增加食物摄入量。在LH，食欲素再次诱导乙醇摄入，而胃饥饿素增加进食量。在NAc，食欲素未能影响乙醇摄入，但确实刺激了食物摄入。
在饮用乙醇的大鼠中，向下丘脑的适当部位注射食欲素或甘丙肽会诱导显著的乙醇摄入而非食物摄入。作为阳性对照的胃饥饿素，在相同的下丘脑部位未能影响乙醇摄入。在作为解剖学对照的NAc，食欲素增加进食量但不增加乙醇摄入量。因此，下丘脑的食欲素和甘丙肽在其他研究表明乙醇和脂肪都会增加内源性肽表达的部位选择性地刺激乙醇摄入。因此，一个随着增加食物摄入量的能力而进化的神经回路显然被乙醇所利用，可能作为酒精滥用的潜在正反馈回路。
