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.