When addiction research was in its infancy roughly a century ago, scientists dismissed substance abuse as a mere personality flaw. Today, addiction is widely thought to be due to complex gene–environment interactions influencing brain function, rather than a simple weakness of character.
In his award address at the 2014 APS Convention, APS William James Fellow Terry E. Robinson (University of Michigan) emphasized that continued research on this interaction would enable psychological scientists and clinicians to more effectively treat those most prone to relapse.
“Temptations typically take the form of cues that are associated with rewards,” Robinson said, but “cues … can only acquire enormous control over behavior and potentially tempt maladaptive behavior” if they become incentive stimuli, which arouse intense feelings and incite us to action.
Robinson explained that for a reward-associated cue to become an incentive stimulus, it has to have acquired “Pavlovian incentive motivational properties,” which have three features. Such cues:
- draw positive attention to themselves — animals are tempted to approach and interact with them;
- become desirable — animals will learn new actions to get them; and
- evoke a conditioned motivational state (“desire”) that can spur animals to seek their associated reward.
Robinson and his collaborators first examined how rats would respond to a food-associated cue and whether that cue would take on the properties of an incentive stimulus. They used a procedure called “autoshaping,” in which the rats were presented with a food cue (a lever) without having to do anything: The lever entered their cage, stayed for 8 seconds, and retracted, after which a food pellet dropped into an adjacent compartment in the cage.
Intriguingly, the researchers found that despite receiving the food without having to perform any action, the rats nevertheless began to do one of two things: Some would approach the lever and interact with it (e.g., biting or scratching it), while others approached the compartment that would eventually contain the food pellet and waited for it. Both groups performed these actions with greater probability, vigor, and speed as the training continued.
Robinson explained that both groups of rats learned the relationship between the cue and the food reward, but learning was manifest in two different conditioned responses: one directed to the cue and the other to the goal. Those who approached the lever are called “sign trackers,” whereas those who directed their attention to the food compartment are “goal trackers.”
“Both sign trackers and goal trackers acquire their respective conditioned responses [approaching and interacting with the lever or food bowl] at exactly the same rate, but only in some animals [the sign trackers] does the conditioned stimulus [the lever] acquire one feature of an incentive stimulus; that is, its ability to attract animals to it.” Interestingly, this predicts whether the reward cue acquires other features of an incentive stimulus. Thus, only in some animals does a conditioned stimulus take on the motivational properties characteristic of an incentive stimulus.
Robinson and his team also wanted to explore the role dopamine would play in the sign-tracking and goal-tracking groups of rats. They followed in the footsteps of APS Fellow Wolfram Schultz, whose classic research on the role of dopamine in monkey learning posits that, when a monkey is primed with a reward-associated cue but does not receive the associated reward, a dopamine response alerts the monkey to the mismatch. This “prediction error signal,” theorized Schultz, is central to the learning process.
“If a phasic dopamine signal is associated with the predictive value of a cue, which is necessary for learning the conditioned stimulus–unconditioned stimulus association, the conditioned stimulus should evoke an equally strong dopamine response in both sign trackers and goal trackers, because both learn this association,” Robinson explained. “However, if the dopamine signal is related to the incentive property of the cue [that only sign trackers learn], then we should see a stronger dopamine response in the sign trackers.”
They found the latter: Presentation of the cue was associated with a phasic dopamine response in rats that approached the lever (sign trackers), but not those that approached the food cup (goal trackers).
In addition, Robinson and his team injected a dopamine blocker into the rats’ brains to assess whether dopamine was necessary for either the acquisition or performance of sign-tracking versus goal-tracking responses. They found the sign trackers stopped interacting with the lever under the influence of the blockers, whereas the goal trackers continued to approach the food dish and wait for a pellet. These studies suggest that dopamine is not necessary for the learning or performance of cue-reward associations per se, but for attributing motivational significance to reward cues.
The researchers were also interested in whether the propensity to attribute motivational value to a food cue would predict such variation in the effects of drug cues, because these are known to produce craving and relapse in addicts. They used a light in lieu of a lever and cocaine in lieu of a food pellet, and as with the previous experiments, only the sign trackers found the drug cue attractive, were drawn close to it, and would work to get it. This suggested that, like the food cue, the drug cue acquired motivational properties to a greater extent in the sign trackers than the goal trackers.
They then asked whether the drug cue would spur drug-seeking behavior (“relapse”) to a greater degree in sign trackers than goal trackers. To do this, they first trained rats to self-administer cocaine by poking their nose into a hole, and the injection of cocaine was paired with illumination of a light in the hole. Next, the researchers introduced an electric current over which the rats would have to cross to reach the cocaine. The current was increased daily, until eventually the rats “became abstinent because of the adverse consequences of continuing to take the drug,” said Robinson. However, when the team reintroduced the flashing light to see whether the rats would be tempted to seek cocaine again, despite the continued negative consequence of doing so, they found that sign trackers were much more likely to brave the electrified floor again. The goal trackers continued to be more wary of the consequences. It was therefore possible for the researchers to predict which rats were most likely to begin “using” drugs again, based on individual variation in the propensity to attribute reward cues with incentive motivational properties.
Robinson and his lab hope their research on drug addiction behavior in rats will spur increased research on individual variation in responsivity to drug cues in humans. Through new research, he concludes, psychological scientists and clinicians can provide the most effective treatment options, which may need to be individualized depending on which kinds of cues provide the greatest temptation to a given person.