Science Watch

Alcoholism, drug abuse, overeating: Psychologists have long sought to understand why we succumb to our temptations, and for good reason. Even those of us who don't have hard-core addictions have trouble curbing our cravings from time to time, whether temptation comes in the form of a cigarette or an ice-cream sundae.

Recently, scientists have inched closer to understanding temptation with the discovery that two distinct motivational behaviors exist in rats—and perhaps in people. Among the rodents, at least, some animals become powerfully attracted to cues that signal an imminent reward, while for others, the cue itself holds no special influence.

Researchers are only just beginning to translate the findings to humans. But if their hunch is correct, the research could open up new avenues for preventing and treating addiction.

"This research highlights the motivational power of cues associated with rewards, such as food or drugs, to instigate maladaptive behavior even in the face of a conscious desire to resist temptation," says Terry Robinson, PhD, professor of psychology and neuroscience at the University of Michigan. "One important target for therapeutic intervention may be the development of effective strategies to cope with the insidious effects of reward-associated stimuli."

Stuck on signals

Years ago, when Rutgers University psychologist Arthur Tomie, PhD, was studying classical conditioning in his lab rats, he noticed something strange. Just as in Ivan Pavlov's famous conditioning experiments, Tomie's model involved a first stimulus that signaled the occurrence of a second stimulus—in this case, a metal lever dropped into the rats' cages, signaling that a food treat was about to appear. The animals quickly learned to connect the signal with the reward, and when the metal lever appeared, many of the rats darted to the corner of the cage where food would be delivered.

Some of the rats, however, were drawn to the lever itself. Rather than run to the food drop, the rats licked and gnawed the inedible metal lever as though it were rat kibble (Clinical Psychology Reviews, 1995). This action wasn't totally unfamiliar, says Tomie. Researchers had noted similar behavior in pigeons back in the 1960s (Journal of the Experimental Analysis of Behavior, 1968). But watching the rats, Tomie was reminded of drug addiction in people. "What intrigued me is that the animals didn't appear to be able to control themselves," Tomie says. He even tried withholding the food reward from those rats that contacted the lever first. Still, a handful of rats couldn't resist the lever's lure. "The animals are unable to stop themselves, to their detriment," he says.

Addiction therapists frequently encounter patients who desperately want to quit drug or alcohol consumption but experience a triggered relapse, Tomie says. For an alcoholic, for example, the trigger may be the sight of a cocktail glass or the flickering neon sign in front of a favored watering hole. Similarly, food-related signals (such as a fast-food sign or TV commercial) often have the power to tempt people even when they aren't hungry.

Studies have shown that obese people are more attracted to food signals than people of healthy weights, Robinson notes. And drug addicts are more likely than non-addicts to be drawn to signals they associate with their habit. "A lot of behavior, be it human or animal, is really controlled by cues in the environment that predict rewards," he says.

Yet it's not clear why some people might be more focused on cues than others, nor how that difference might contribute to addictions or overeating. That's where the rodents can help, Robinson believes. Over the last several years, he has used a rat model similar to Tomie's to explore why some animals are so easily tempted by signals in their environments.

Different brains

Robinson has identified two distinct behaviors among the rodents. For some rats (the "goal-trackers") the final reward is most important. They run for the food cup as soon as they spot the signaling lever. For others (the "sign-trackers") the cue itself holds the most sway. These are the animals that Tomie saw licking and gnawing on the lever.

The sign trackers seem to be particularly prone to addiction or other maladaptive behaviors, Robinson says. Rodents that keep their eyes on the lever are much more likely to seek drugs or swallow alcohol from a sipper.

A compulsion for cues seems to extend across many types of behaviors. Sign-tracking rats have trouble resisting cues in general, whether they're associated with food or with drugs, such as cocaine. In fact, by identifying sign-trackers using the food-pellet model, Robinson can take rats that have never been exposed to drugs and correctly predict which animals are likely to exhibit drug-seeking behaviors when introduced to cocaine (Biological Psychiatry, 2010).

This dark side of sign tracking may be especially worrisome given that the behavior isn't all that unusual. Over the years, Robinson has amassed data on close to 2,000 rats. About a third of them exhibit sign-tracking behavior, while a third engage in goal tracking. (The remaining third vacillate back and forth, and aren't easily classified as members of either group.) In other words, sign tracking—and the potentially problematic behaviors associated with it—appear to be quite common in the rat world. "We're not talking about a few extremes," he says. "We're actually talking about a large proportion of the population."

What makes signs and symbols so powerful for this group of animals? To answer that question, Robinson has begun looking more deeply into the brain's reward system. In a study last year, he and his colleagues discovered that when sign-trackers glimpse a cue, they experience a rapid spike in dopamine, the neurotransmitter that helps control the brain's reward center. Goal-trackers don't show that spike (Nature, 2011). "One hypothesis is that, for whatever reason, these animals have different brains," he says. "The behavior of sign-trackers is strongly controlled by dopamine-dependent motivational processes. But in the goal trackers, something else is going on psychologically."

So far, it's not clear what that something might be. Robinson's hypothesis is that for goal-trackers, the cue evokes a more cognitive expectation process that does not require dopamine and that leads the animal to the expected reward. There's some evidence that the tendency to become a sign-tracker or a goal-tracker is heritable, Robinson says (Neuropsychopharmacology, 2010). But, he adds, "we know almost nothing about the genetic basis."

However, there's also evidence that early environmental experiences can predispose a rat pup to a future of sign- or goal-tracking. Pups reared in stressful environments without their mothers are more likely to become sign-trackers as adults (Behavioural Brain Research, 2011). "As you'd expect with any complex psychological trait, it's influenced by the interaction between environmental and genetic factors," he says.

Air-popped rewards

To date, most of the work on sign-tracking has been done in rats. But there are some emerging hints that the same patterns may show up in people. In a small study of 15 adult smokers, Stephen Mahler, PhD, at the Medical University of South Carolina, and Harriet de Wit, PhD, at the University of Chicago, found that participants who experienced potent cue-induced cravings for cigarettes also reacted more strongly to food-related images than those who didn't experience such cravings (PLoS One, 2010). In humans as in rats, some people may be highly sensitive to conditioned stimuli.

Margaret Wardle, PhD, a postdoctoral researcher in DeWit's lab, is looking further into sign-tracking by conditioning people with food rewards. In her experiment, she is presenting hungry volunteers with neutral images, such as nature scenes, on a computer screen. That cue is paired with a reward of popcorn delivered through plastic tubes. Later, Wardle shows volunteers a series of images and measures their affinity for pictures that were previously paired with popcorn.

The research isn't without its difficulties. "There are some challenges in moving this over to people," Wardle says. "People don't usually approach or lick or bite things that they're attracted to." Instead, she gauges interest in cues in more subtle ways. Using sensors attached to the volunteers' faces, she measures the activity of barely detectible facial movements. (The zygomatic muscle involved with smiling, for instance, activates slightly when you're looking at something you desire.)

Wardle is also tracking reaction time and eye gaze. "The idea is that sign-trackers will maintain their attention on the [images paired with food], whereas goal-trackers will not," she says.

This study is just a first pass—"a real rough cut," Wardle says—to see whether human sign-trackers can be reliably identified in lab studies. If she's successful, it could lead to a lifetime's worth of follow-up studies. "My hope is that if we can identify this trait in a lab, we can start to build a picture of what a sign-tracking human looks like out in the real world. How does this relate to vulnerability to drug use?" she says.

Understanding these behaviors outside the lab will be challenging, since cues and rewards are often so closely linked in human life; out in the real world, it's hard to separate the cocktail glass from the martini it holds. Still, Wardle is hopeful. "In the future we'd like to do things like look at adolescents, who have comparatively little drug exposure, to see if we can predict going forward who is going to have what kind of behavior," she says.

That's precisely where Robinson hopes his animal studies will lead. "We're interested in predicting who is going to be prone to obesity or prone to addiction," he says. That predictive power might one day lead to interventions that help prevent people from developing the maladaptive behaviors in the first place. The work could also lead to new treatments. Sign-trackers dealing with addiction, for example, might benefit from therapies that emphasize avoiding cues. "A better understanding of the neurobiological processes by which cues gain control over behavior may reveal other treatment strategies," Robinson says.

Plenty of dots remain to be connected between lever-gnawing rats and people addicted to food, drugs, alcohol or tobacco. But the research is really taking off, Tomie says. "There's a lot of interest right now in the addiction world about sign-tracking," he says. "It's starting to move from the background to the foreground."

Kirsten Weir is a writer in Minneapolis.