To err—and therefore, to regret—is human. Now, a new study suggests that rodents are also capable of pining over what might have been. Researchers say the insight could help improve animal models of bad decisions, such as drug or alcohol use that leads to addiction.

Our ability to experience regret depends on what neuroscientists describe as “mental time travel”—casting our thoughts into the past or future to reconstruct or fabricate scenarios, says A. David Redish, a neuroscientist at the University of Minnesota, Twin Cities. Although researchers once thought this ability was unique to primates and humans, Redish’s lab and other groups have demonstrated that rodents also perform a kind of mental time travel as they learn to navigate through mazes. Before making decisions about which way to turn, for example, rats pause to retrace their steps by reactivating patterns of brain activity established in previous explorations.

Still, when graduate student Adam Steiner told Redish that rodents in his lab appeared to be glancing wistfully back at a location where they’d missed an opportunity for a favorite meal, calling the behavior “regret” seemed far-fetched, Redish says. For one thing, the animals could just as easily have been displaying disappointment when their expectations of getting a treat were dashed, he says. To qualify as regret, Steiner needed to demonstrate that the animals recognized that their misfortune had resulted directly from their own errors.

So Steiner and Redish devised a task involving a circular runway with four spokes and called it “Restaurant Row.” They placed feeding machines that dispensed different flavored food pellets at the end of each spoke: cherry, chocolate, banana, or plain. (Preferences vary by rodent.) Each rat was given 1 hour per day to feed, and its task was to figure out how to get as much to eat as possible.

As the rats became accustomed to Restaurant Row, they learned that a tone indicated how long they would have to wait for their pellets to be dispensed at any given spoke—a randomly selected interval of between 1 and 45 seconds. A higher pitch meant a longer delay, and it was up to the rats to decide if the wait was worth it. If they moved on, the countdown would stop and the offer of food was rescinded.

To test whether the animals experienced regret, Redish and Steiner watched the rats keenly on the occasions when they left one restaurant hungry only to wait even longer at the next one. If the rat had left a restaurant that had a wait above its established threshold and then had to wait again at the next stop, it was a reasonable decision and should merely inspire disappointment, not regret, they hypothesized. After all, the animal had made a reasonable decision to move on to the next stop on the restaurant wheel after a lengthy wait yielded nothing. But if the rat had left a restaurant with a waiting time below its threshold—only to encounter a far longer wait at the next spoke, it had made a bona fide error of judgment, and regret would be appropriate.

As predicted, the rats behaved differently in disappointing, versus regrettable, scenarios, the team reports this month in Nature Neuroscience. In the disappointing scenarios, the animals looked toward their own meals, or sometimes toward the next restaurant. Under more regrettable conditions, the rats did indeed cast wistful-seeming backward glances toward the previous spoke. “It was like Homer Simpson going, 'D’oh!,' ” Redish says.

The next task was to determine what was going on inside the rodents’ brains. Redish and Steiner implanted minute electrodes into a brain region associated with regret in monkeys and humans, called the orbitofrontal cortex (OFC). People with damage in this area often do not experience regret, Redish notes.

Using a computer algorithm trained to decode the rats’ neural activity, the team found that neurons in the OFC fired in a pattern associated with the previous restaurant when the rats were looking backward, suggesting that the rodents were indeed preoccupied with what might have been, Redish says. Lingering on past errors didn’t seem to improve the rats’ future choices. Instead of skipping the long wait in the new restaurant and trying a third option, they tended to stick it out, he says.

Understanding the subtleties that underlie decision-making in rodents could help researchers who study addiction develop better models, Redish says. At its core, addiction represents decision-making gone wrong, he says.

The researchers did a “great job” of designing a task that can discriminate between the regret of making a poor decision and the disappointment that results when one is punished despite making all the right choices, says Alex Vaughan, a neuroscientist at Cold Spring Harbor Laboratory in New York. The task also nicely mimicked the types of decisions animals must make as they forage in the wild, he notes.

A vital next question is how information about regret encoded by neurons in the OFC influences decision-making in the rest of the brain, Vaughan says. “The OFC appears to carry a lot of varied information,” he notes, and although the activity that Redish and colleagues detected is intriguing, “discovering whether and how the animal uses each kind of information in other parts of the brain is still very much an ongoing task in the field.”