3. Individual differences in the attribution of incentive salience to cues
It has long been known that a food-paired cue (conditioned stimulus; CS) that has been repeatedly paired with food reward will reliably elicit a conditioned response in rats. However, it is also true that the form of the conditioned response can vary due to individual differences, with some rats approaching and interacting with the cue itself (“sign trackers”, STs) and some approaching the site of impending food delivery (“goal trackers”, GTs). In the standard conditioning procedure used to determine sign- and goal-tracking tendencies (Flagel et al. 2009; Meyer et al. 2012; Tomie et al. 2012), a retractable lever is used as the CS. In each trial (i.e. CS-reward pairing) the lever-CS is inserted into the cage for 8s, then is retracted and a banana pellet is immediately dispensed. The reward is delivered non-contingently and is independent of any action by the rat. Rats are categorized as STs or GTs based on whether they preferentially contact the lever or the food cup during the performance of their conditioned response (Meyer et al. 2012).
For both STs and GTs the CS acquires predictive value; however, only for STs does the CS also acquire incentive value, which causes STs, but not GTs, to become attracted to the lever and interact with it when it is present. By predictive value, we mean the learning of associations and the cognitive expectation of reward; in other words, an animal understands that the CS predicts the rewar d and reacts with a conditioned response. By incentive value, we mean that not only does a cue elicit the cognitive expectation of reward; it also elicits a dopamine-mediated motivational state akin to craving, which in rats can be expressed as desire for the cue itself (Flagel et al. 2009; Robinson et al. 2014; Saunders and Robinson 2013; Singer et al. 2016a; Singer et al. 2016b). This tendency to attribute incentive salience to a CS makes STs more susceptible to the motivational attraction of cues than GTs (Flagel et al. 2009; Saunders and Robinson 2013). As a result, STs work harder than GTs to gain access to the CS in a conditioned reinforcement paradigm (Beckmann and Chow 2015; Lomanowska et al. 2011; Robinson and Flagel 2009), STs are more resistant to Pavlovian extinction than GTs (Ahrens et al. 2016b), and discrete cues elicit greater reinstatement of food- and drug seeking behaviors in STs than GTs (Saunders and Robinson 2010, 2013; Yager and Robinson 2010, 2013).
Genetic differences underlie many of the traits that predispose STs to be more attracted to cues than GTs. Selective breeding for addiction-related traits also co-selects for the associated ST versus GT tendencies (Flagel et al. 2010), and certain commercial vendor colonies are more likely to produce STs than others (Fitzpatrick et al. 2013). The differences between STs and GTs are associated with other psychological tendencies that are not directly related to cue responses but may contribute to individual vulnerability to addiction. Compared to GTs, STs are more impulsive (Lovic et al. 2011), have diminished attentional control and reduced cholinergic activity in the prefrontal cortex (Koshy Cherian et al. 2017; Paolone et al. 2013), show greater locomotor reactivity to a novel environment (Flagel et al. 2010), show altered dopamine regulation even in the absence of rewarding stimuli (Flagel et al. 2010; Singer et al. 2016b), show greater expression of conditioned fear (Morrow et al. 2011; Morrow et al. 2015), and are more susceptible to incentive motivation during adolescence compared to adulthood (DeAngeli et al. 2017).
Sleep disturbances can strongly influence the expression of many of the behaviors that differ between STs and GTs, such as attentional control and impulsivity (Pilcher et al. 2015), and can alter dopamine activity (Volkow et al. 2008; Volkow et al. 2012; Wiers et al. 2016) and responses to drug-paired cues (Chen et al. 2015; Puhl et al. 2013; Volkow et al. 2012). However, the direct relationship between sleep and ST/GT behavior has never been studied. Given the existing literature, we predict that SD will impact these two groups differently, particularly with regard to cue- or drug-induced motivation, as well as other measures of reward-seeking behavior. Given the dramatic differences in their cholinergic and dopaminergic circuitry (Flagel and Robinson 2017; Pitchers et al. 2017), it is also likely that STs and GTs will show differences in their baseline sleep duration and sleep architecture, as well as differences in the precise nature of sleep disturbances caused by drug exposure or environmental stressors.
We next discuss the precise neural circuits (Fig. 1) that are simultaneously involved in regulating sleep/wake states as well as encoding the responses to drug- and reward-related cues. As we point out, many of these structures have already been found to be differentially activated in sign-trackers vs goal-trackers, further highlighting their potentially crucial role in explaining individual differences linking sleep and addiction.