Orexigenic peptides and alcohol intake: differential effects of orexin, galanin, and ghrelin.
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.
Schneider
Eve R
ER
Department of Psychology, Princeton University, Princeton, New Jersey 08544, USA.
Rada
Pedro
P
Darby
Ryan D
RD
Leibowitz
Sarah F
SF
Hoebel
Bartley G
BG
D000428:Alcohol Drinking / Q000503:physiopathology*; D000818:Animals; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D019004:Galanin / Q000502:physiology*; D054439:Ghrelin / Q000502:physiology*; D007026:Hypothalamic Area, Lateral / Q000187:drug effects / Q000502:physiology; D007267:Injections; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008297:Male; D009479:Neuropeptides / Q000502:physiology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D000068797:Orexins; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D002492:Central Nervous System Depressants; D054439:Ghrelin; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D000431:Ethanol; D019004:Galanin