Publications

Drugs of abuse acquire different degrees of control over thoughts and actions based not only on the effects of drugs themselves, but also on predispositions of the individual. Those individuals who become addicted are unable to shift their thoughts and actions away from drugs and drug-associated stimuli. Thus in addicts, exposure to places or things (cues) that has been previously associated with drug-taking often instigates renewed drug-taking. We and others have postulated that drug-associated cues acquire the ability to maintain and instigate drug-taking behavior in part because they acquire incentive motivational properties through Pavlovian (stimulus–stimulus) learning. In the case of compulsive behavioral disorders, including addiction, such cues may be attributed with pathological incentive value (“incentive salience”). For this reason, we have recently begun to explore individual differences in the tendency to attribute incentive salience to cues that predict rewards. When discrete cues are associated with the non-contingent delivery of food or drug rewards some animals come to quickly approach and engage the cue even if it is located at a distance from where the reward will be delivered. In these animals the reward-predictive cue itself becomes attractive, eliciting approach towards it, presumably because it is attributed with incentive salience. Animals that develop this type of conditional response are called “sign-trackers”. Other animals, “goal-trackers”, do not approach the reward-predictive cue, but upon cue presentation they immediately go to the location where food will be delivered (the “goal”). For goal-trackers the reward-predictive cue is not attractive, presumably because it is not attributed with incentive salience. We review here preliminary data suggesting that these individual differences in the tendency to attribute incentive salience to cues predictive of reward may confer vulnerability or resistance to compulsive behavioral disorders, including addiction. It will be important, therefore, to study how environmental, neurobiological and genetic interactions determine the extent to which individuals attribute incentive value to reward-predictive stimuli.

If presentation of a stimulus (conditional stimulus, CS) reliably predicts delivery of a reward, the CS will come to evoke a conditional response (CR) through Pavlovian learning, and the CS may also acquire incentive motivational properties. Thus, CSs can have both predictive and incentive properties. We ask here whether it is possible to dissociate the predictive versus incentive properties of a CS in rats by considering individual differences in the nature of the CR.

The neurobiological bases of increased vulnerability to substance abuse remain obscure. We report here that rats that were selectively bred for greater drug-seeking behavior exhibited higher levels of FGF2 gene expression. We then asked whether a single FGF2 administration (20 ng/g, s.c.) on postnatal day 2 (PND2) can have a lifelong impact on drug-taking behavior, spatial and appetitive learning and the dopaminergic system. Indeed, early life FGF2 enhanced the acquisition of cocaine self-administration in adulthood. However, early life FGF2 did not alter spatial or operant learning in adulthood. Furthermore, early life FGF2 did not alter gene expression in the dopaminergic system in adulthood. These results suggest that elevated levels of FGF2 may lead to increased drug-taking behavior without altering learning. Thus, FGF2 may be an antecedent of vulnerability for drug-taking behavior and may provide clues to novel therapeutic approaches for the treatment of addiction.