Genetic Studies of Incentive Salience
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.
Methods for genotype
Genotypes were generated as described in [PMID: 23979941, DOI: 10.1534/g3.113.007948]
Methods for Phenotypes
Cocaine Contextual Conditioning:Rats are injected with cocaine and then placed into a chamber with novel features thatcan be associated with the cocaine experience. On the final test day, they are placed into the chambers without cocaine on board.
Novelty seekingRats are habituated to a grid chamber floor, similar to the floors they experienced in conditioning chambers used previously. After two days of habituation, half of the floor will be replaced with a novel floor type for a third, test day. This test allows us to assess the effects of phenotype and sex on the rats’ propensity to investigate novel environments.
Pavlovian Conditioned Approach:To examine individual differences in the propensity to attribute incentive salience to reward cues, HS rats will first be exposed to a Pavlovian conditioning paradigm wherein a cue (lever) is repeatedly paired with presentation of a reward (food). We have previously demonstrated that 3 different phenotypes emerge following Pavlovian training in this manner. Sign trackers are those who come to approach and manipulate the cue upon its presentation, goal trackers are those who god to the food cup upon cue presentation, and intermediate responders vacillate between the cue and location of reward delivery. Thus, for sign trackers, the cue becomes imbued with incentive motivational value, or incentive salience; whereas for goal trackers, the cue serves merely as a predictor of impending reward deliver.
Methods for Omics