This research was supported by USPHS Grant AA12882 and the Lane Foundation.
Orexigenic Peptides and Alcohol Intake: Differential Effects of Orexin, Galanin, and Ghrelin
Article first published online: 11 SEP 2007
Alcoholism: Clinical and Experimental Research
Volume 31, Issue 11, pages 1858–1865, November 2007
How to Cite
Schneider, E. R., Rada, P., Darby, R. D., Leibowitz, S. F. and Hoebel, B. G. (2007), Orexigenic Peptides and Alcohol Intake: Differential Effects of Orexin, Galanin, and Ghrelin. Alcoholism: Clinical and Experimental Research, 31: 1858–1865. doi: 10.1111/j.1530-0277.2007.00510.x
- Issue published online: 17 SEP 2007
- Article first published online: 11 SEP 2007
- Received for publication January 25, 2007; accepted August 2, 2007.
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.