Sign Trackers Research Articles

Individual differences in the influence of task-irrelevant Pavlovian cues on human behavior.

Pavlovian-to-instrumental transfer (PIT) refers to the process of a Pavlovian reward-paired cue acquiring incentive motivational proprieties that drive choices. It represents a crucial phenomenon for understanding cue-controlled behavior, and it has both adaptive and maladaptive implications (i.e., drug-taking). In animals, individual differences in the degree to which such cues bias performance have been identified in two types of individuals that exhibit distinct Conditioned Responses (CR) during Pavlovian conditioning: Sign-Trackers (ST) and Goal-Trackers (GT). Using an appetitive PIT procedure with a monetary reward, the present study investigated, for the first time, the extent to which such individual differences might affect the influence of reward-paired cues in humans. In a first task, participants learned an instrumental response leading to reward; then, in a second task, a visual Pavlovian cue was associated with the same reward; finally, in a third task, PIT was tested by measuring the preference for the reward-paired instrumental response when the task-irrelevant reward-paired cue was presented, in the absence of the reward itself. In ST individuals, but not in GT individuals, reward-related cues biased behavior, resulting in an increased likelihood to perform the instrumental response independently paired with the same reward when presented with the task-irrelevant reward-paired cue, even if the reward itself was no longer available (i.e., stronger PIT effect). This finding has important implications for developing individualized treatment for maladaptive behaviors, such as addiction.

Dopamine D2 Modulation of Sign and Goal Tracking in Rats.

In Pavlovian conditioning, sign- and goal-tracking behaviors represent different approaches towards the conditioned stimulus. These behavioral patterns have been associated with predictive or incentive properties of the conditioned stimulus, with a crucial involvement of the mesolimbic dopamine system. As it is possible that sign tracking behavior is more sensitive to dopamine modulation, we evaluated the dopamine-dependence of sign- and goal-tracking behavior. We assessed responses to both a D2 agonist and an antagonist, and tested performance in a behavioral paradigm known to activate dopamine projections and in an animal model that affects mesolimbic and mesocortical function. Sign trackers displayed a greater sensitivity to a D2 agonist and smaller prepulse inhibition of the acoustic startle response than goal trackers, suggesting a reduced inhibitory ability. In addition, a neonatal ventral hippocampal lesion resulted in the loss of incentive salience of cues in sign trackers. Overall, these data indicate that sign-tracking behavior is more heavily controlled by dopamine than goal tracking.

High locomotor reactivity to novelty is associated with an increased propensity to choose saccharin over cocaine: new insights into the vulnerability to addiction.

Drug addiction is associated with a relative devaluation of natural or socially-valued reinforcers that are unable to divert addicts from seeking and consuming the drug. Before protracted drug exposure, most rats prefer natural rewards, such as saccharin, over cocaine. However, a subpopulation of animals prefer cocaine over natural rewards and are thought to be vulnerable to addiction. Specific behavioral traits have been associated with different dimensions of drug addiction. For example, anxiety predicts loss of control over drug intake whereas sensation seeking and sign-tracking are markers of a greater sensitivity to the rewarding properties of the drug. However, how these behavioral traits predict the disinterest for natural reinforcers remains unknown. In a population of rats, we identified sensation seekers (HR) on the basis of elevated novelty-induced locomotor reactivity, high anxious rats (HA) based on the propensity to avoid open arms in an elevated-plus maze and sign-trackers (ST) that are prone to approach, and interaction with, reward-associated stimuli. Rats were then tested on their preference for saccharin over cocaine in a discrete-trial choice procedure. We show that HR rats display a greater preference for saccharin over cocaine compared with ST and HA whereas the motivation for the drug was comparable between the three groups. The present data suggest that high locomotor reactivity to novelty, or sensation seeking, by predisposing to an increased choice toward non-drug rewards at early stages of drug use history, may prevent the establishment of chronic cocaine use.

Pavlovian conditioning and cross-sensitization studies raise challenges to the hypothesis that overeating is an addictive behavior

Elevated glucocorticoid levels and sign tracking (ST) in Pavlovian conditioning are potential biomarkers of compulsive behaviors such as addiction. As overeating is sometimes viewed as a form of addictive behavior, we hypothesized that murine Pavlovian sign trackers would have a greater propensity to overeat and develop obesity. Using a food reward in the classical conditioning paradigm, we show that ST behavior is a robust conditioned response but not a predictor of eating and growth trajectories in mice, thus challenging the view that the development of obesity and drug addiction depend on identical mechanisms. This interpretation was supported by experiments which showed that overweight mice do not display cross-sensitization to an addictive drug (morphine), and conversely, that overweight morphine-sensitized animals do not overconsume a highly rewarding food. Although the rewarding/motivational effects of both food and drugs of abuse are mediated by similar neurochemical mechanisms, obesity and drug addiction represent a summation of other dysfunctional input and output pathways that lead to the emergence of two distinct disorders, each of which would deserve a specific pharmacotherapeutic approach.

Cholinergic Control over Attention in Rats Prone to Attribute Incentive Salience to Reward Cues

Some rats [sign-trackers (STs)] are especially prone to attribute incentive salience to reward cues, relative to others [goal-trackers (GTs)]. Thus, reward cues are more likely to promote maladaptive reward-seeking behavior in STs than GTs. Here, we asked whether STs and GTs differ on another trait that can contribute to poor restraint over behavior evoked by reward cues. We report that, relative to GTs, STs have poor control over attentional performance, due in part to insufficient cholinergic stimulation of cortical circuitry. We found that, relative to GTs, STs showed poor performance on a sustained attention task (SAT). Furthermore, their performance fluctuated rapidly between periods of good to near-chance performance. This finding was reproduced using a separate cohort of rats. As demonstrated earlier, performance on the SAT was associated with increases in extracellular levels of cortical acetylcholine (ACh); however, SAT performance-associated increases in ACh levels were significantly attenuated in STs relative to GTs. Consistent with the view that the modulatory effects of ACh involve stimulation of α4β2* nicotinic ACh receptors (nAChRs), systemic administration of the partial nAChR agonist ABT-089 improved SAT performance in STs and abolished the difference between SAT-associated ACh levels in STs and GTs. Neither the nonselective nAChR agonist nicotine nor the psychostimulant amphetamine improved SAT performance. These findings suggest that individuals who have a propensity to attribute high-incentive salience to reward cues also exhibit relatively poor attentional control. A combination of these traits may render individuals especially vulnerable to disorders, such as obesity and addiction.

A cocaine cue is more preferred and evokes more frequency-modulated 50-kHz ultrasonic vocalizations in rats prone to attribute incentive salience to a food cue.

Individuals vary considerably in the extent to which they attribute incentive salience to food-associated cues. We asked whether individuals prone to attribute incentive salience to a food cue are also prone to attribute incentive properties to a stimulus associated with a drug of abuse-cocaine. We first identified those rats that attributed incentive salience to a food cue by quantifying the extent to which they came to approach and engage a food cue. We then used a conditioned place preference procedure to pair an injection of 10 mg/kg cocaine (i.p.) with one distinct floor texture (grid or holes) and saline with another. Following 8 days of conditioning, each rat was given a saline injection and placed into a chamber that had both floors present. We measured the time spent on each floor, and also 50-kHz ultrasonic vocalizations, which have been associated with positive affective states. Rats that vigorously engaged the food cue ("sign trackers") expressed a preference for the cocaine-paired floor compared to those that did not ("goal trackers"). In addition, sign trackers made substantially more frequency-modulated 50-kHz vocalizations when injected with cocaine and when later exposed to the cocaine cue. Rats prone to attribute incentive salience to a food cue are also prone to attribute incentive motivational properties to a tactile cue associated with cocaine. We suggest that individuals prone to attribute incentive salience to reward cues will have difficulty resisting them and, therefore, may be especially vulnerable to develop impulse control disorders, including addiction.

Individual differences in the propensity to approach signals vs goals promote different adaptations in the dopamine system of rats

The way an individual responds to cues associated with rewards may be a key determinant of vulnerability to compulsive behavioral disorders. We studied individual differences in Pavlovian conditioned approach behavior and examined the expression of neurobiological markers associated with the dopaminergic system, the same neural system implicated in incentive motivational processes. Pavlovian autoshaping procedures consisted of the brief presentation of an illuminated retractable lever (conditioned stimulus) followed by the response-independent delivery of a food pellet (unconditioned stimulus), which lead to a Pavlovian conditioned response. In situ hybridization was performed on brains obtained either following the first or last (fifth) day of training. Two phenotypes emerged. Sign-trackers (ST) exhibited behavior that seemed to be largely controlled by the cue that signaled impending reward delivery; whereas goal-trackers (GT) preferentially approached the location where the reward was delivered. Following a single training session, ST showed greater expression of dopamine D1 receptor mRNA relative to GT. After 5 days of training, GT exhibited greater expression levels of tyrosine hydroxylase, dopamine transporter, and dopamine D2 receptor mRNA relative to ST. These findings suggest that the development of approach behavior towards signals vs goal leads to distinct adaptations in the dopamine system. The sign-tracker vs goal-tracker phenotype may prove to be a valuable animal model to investigate individual differences in the way incentive salience is attributed to environmental stimuli, which may contribute to the development of addiction and other compulsive behavioral disorders.