Preclinical studies shed light on individual variation in addiction vulnerability

Cues associated with drug use attract the attention of addicts, draw them to locations where drugs are located, and motivate drug-seeking—often leading to relapse—even in the face of an expressed desire to remain abstinent. There is, however, considerable individual variation in the ability of reward cues to gain motivational control over behavior. Emerging evidence from preclinical studies suggests that such variation is due, at least in part, to intrinsic differences in the extent to which reward cues are attributed with incentive salience, thereby acquiring the properties of incentive stimuli. When a Pavlovian conditional stimulus (CS) reliably predicts delivery of a food reward, for some rats (sign-trackers; STs), the CS itself becomes attractive, in that these rats approach and interact with the CS, and becomes ‘wanted', in that these rats will work just to obtain the CS. For other rats (goal-trackers; GTs), the CS itself is not attractive, but instead evokes conditioned approach towards the location of food delivery (rather than the CS), and GTs will not work avidly to get the CS (Meyer et al, 2012). Importantly, variation in the propensity to attribute incentive salience to a food cue predicts the extent to which drug cues gain motivational control over behavior. For example, a cocaine-associated cue is more effective in maintaining self-administration behavior, and instigates more robust relapse behavior, in STs than GTs (Saunders and Robinson, 2010). Additionally, STs will exert more effort to self-administer cocaine, and are more likely to relapse when ‘primed' with drugs themselves (Saunders and Robinson, 2011). Therefore, it is possible to predict, before any drug experience, which rats will find drug cues more desirable, will exhibit greater motivation to take drugs, and will be more likely to relapse. Thus, the extent to which drugs cues acquire motivational properties may not only influence their ability to control normal behavior but to also tempt maladaptive behavior, thereby contributing to addiction vulnerability. Several lines of evidence suggest that the propensity to attribute incentive salience to reward cues represents a complex psychological trait (Meyer et al, 2012). First, there are neurobiological differences between STs and GTs, including differences in dopaminergic systems (Flagel et al, 2011; Flagel et al, 2010). Second, the variation is heritable (Flagel et al, 2010), indicating that some unknown genetic differences contribute to variation in reward cue processing. Third, the extent to which rats become STs or GTs is influenced by early life experiences (Lomanowska et al, 2011), suggesting that environmental factors also contribute to how individuals process and respond to reward cues in adulthood. In conclusion, this line of research provides a novel approach to understanding the interplay between genetic, epigenetic, environmental, and neural-systems-level factors that confer susceptibility (and resilience) to impulse-control disorders, such as addiction. Implications for the development of clinical intervention strategies include: (1) greater attention to individual differences in the psychological factors that control pathological motivation for drugs, and (2) greater recognition that, in susceptible individuals, drug cues may be especially insidious in instigating and maintaining drug-seeking behavior.