Researchers at the University of Texas (UT) Southwestern Medical Center (Dallas, USA) assessed the effects of different pharmacological, physiological, and genetic models of increased ghrelin and ghrelin-signaling blockade on two classic behavioral tests of reward behavior in mice: conditioned place preference (CPP), and operant conditioning. In the first, they evaluated whether mice that were fully sated preferred a room where they had previously found high-fat food over one that had only offered regular, bland food. They found that when mice in this situation were administered ghrelin, they strongly preferred the room that had been paired with the high-fat diet. Mice without ghrelin, on the other hand, showed no preference. The researchers also found that blocking the action of ghrelin prevented the mice from spending as much time in the room they associated with the high-fat food. In the second test, the researchers observed how long mice would continue to poke their snout into a hole in order to receive a pellet of high-fat food. They found that the mice that did not receive ghrelin gave up much sooner than the ones that did receive ghrelin. The study was published ahead of print on December 23, 2009, in Biological Psychiatry.

"What we show is that there may be situations where we are driven to seek out and eat very rewarding foods, even if we're full, for no other reason than our brain tells us to,” said lead author Jeffrey Zigman, M.D., a UT assistant professor of internal medicine and psychiatry.

Ghrelin is a potent orexigenic hormone that is considered the counterpart of the hormone leptin (produced by adipose tissue), which induces satiation when present at higher levels. Ghrelin is produced mainly by cells lining the fundus of the human stomach and by the epsilon cells of the pancreas, and activates cells in the arcuate nucleus that include the orexigenic neuropeptide Y (NPY) neurons; Ghrelin-responsiveness of these neurones is both leptin- and insulin-sensitive. Ghrelin also activates the mesolimbic cholinergic-dopaminergic reward link, a circuit that communicates the hedonic and reinforcing aspects of natural rewards, such as food, as well as of addictive drugs, such as ethanol.

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