P50: Genetic Studies of Incentive Salience

Research Project 1: Summary

Stimuli (cues) in the environment associated with reward can motivate normal behavior, bringing one in close proximity to valuable resources (i.e. food, water, mates); but they can also gain inordinate control over behavior, as is the case with addiction. The ability of reward cues to motivate both normal and maladaptive behavior occurs through Pavlovian learning processes. Thus, when a cue is repeatedly paired with presentation of a reward, it can acquire the ability to act as a predictor, but can also acquire incentive motivational properties. For example, in addicts, cues that have been previously associated with the drug taking experience acquire the ability to maintain drug-seeking behavior and instigate relapse, even when there is a strong desire to stop use. We have recently discovered that in rats there is considerable individual variation in the extent to which food cues are attributed with Pavlovian incentive motivational value (“incentive salience”) and this variation predicts how avidly they will later seek drugs and the propensity to relapse. Using a Pavlovian conditioning paradigm, rats can be classified as sign-trackers—those that attribute incentive salience to reward cues; goal-trackers—those that assign only predictive value to reward cues; or intermediate responders—those that show neither clear sign- nor goal-tracking behavior. Here we will exploit this natural variation in a population of heterogeneous stock rats (N:NIH-HS), which provide the means to study the genetics underlying individual differences in the propensity to attribute incentive salience to reward cues. In addition, we will examine the role of gender in these individual differences and also assess the relationship among a number of other addiction-related behavioral traits and associated genetic differences. This work has the potential to uncover genes that contribute to vulnerability to addiction.

Experimental protocols:

Cocaine Contextual Conditioning

Novelty seeking

Pavlovian Conditioned Approach