According to the Organisation for Economic Co-operation and Development (OECD) report, ‘Obesity and the Economics of Prevention: Fit not Fat’, published in 2010, one person out of every 10, or 500 million people worldwide, is defined as obese. In order to understand the motivation behind empty eating – the tendency of animals to over-indulge when they do not physiologically require additional calories – scientists are investigating the body's natural mechanisms for evaluating satiation and hunger. In a recent study published in Current Biology, a group of scientists from the University of Michigan, USA, contribute to our understanding of over-eating by reporting that they have found a highly targeted brain region, the anteromedial quadrant of the dorsal neostriatum, where an opioid neuropeptide, enkephalin, serves as a signal to eat.

Based on previous work implicating the dorsal neostriatum as a region involved in reward and addiction, Alexandra Difeliceantonio, Omar Mabrouk, Robert Kennedy and Kent Berridge designed a study to measure the neuropeptides that are naturally released in rat brains during eating. In order to measure peptide release, the team implanted probes in the dorsal neostriatum of the rodents and measured the extracellular levels of neuropeptides (including enkephalin) while the rats consumed chocolate candies.

The team found that compared with the baseline measurements – taken before a meal in mildly hungry rats – the enkephalin measurements of the chocolate-consuming rats reached 150% of the pre-meal levels and remained elevated while they ate. Furthermore, they found that the faster the rat began consuming its first chocolate, the higher the relative increase in enkephalin. Intrigued by the possibility that enkephalin might stimulate the rats to over-eat, the team performed microinjections of a synthetic opioid peptide, DAMGO, into different sites within the dorsal neostriatum region of the brain to mimic enkephalin and monitored the rat's appetites. The DAMGO injections, specifically within the anteromedial quadrant of the dorsal neostriatum, proved to produce the most intense over-consumption of chocolate, with the rats increasing their intake by more than 250% compared with rats that had received no DAMGO.

Next, the team wondered whether the rats were actually enjoying their sweet over-indulgence following the DAMGO injection. By measuring the rodent's reactions to their diet of chocolate (including rhythmic tongue extensions and lip licking, typical responses to sweetness and pleasure), the team was able to quantify their responses to find out how much they were enjoying their chocolate binge. Interestingly, they found that DAMGO microinjections into the dorsal neostriatum region of the brain failed to elicit the stereotypical set of ‘liking’ reactions typical for sweet tastes: the rats were not enjoying the chocolates as they over-indulged. In fact, whether the team used sucrose solution infused directly into the mouth or actual chocolates, they could not make the rats that had been treated with DAMGO behave as though they were enjoying the experience when eating, demonstrating that as the rats gorged they failed to derive any gratification from it. Essentially, enkephalin was stimulating the rats to over-eat, but their over-indulgence gave them no pleasure.

Berridge's exciting report has in essence begun the meticulous mapping of the mammalian brains' relationship to food; by finding where the neuro-chemical signaling of wanting but not enjoyment resides, their work helps to pinpoint the empty eating at the heart of the current obesity crisis.

A. G.
O. S.
R. T.
K. C.
Enkephalin surges in dorsal neostriatum as a signal to eat
Curr. Biol.