Sign-tracking

Midbrain and striatal dopamine signals have been extremely well characterized over the past several decades, yet novel dopamine signals and functions in reward learning and motivation continue to emerge. A similar characterization of real-time sub-second dopamine signals in areas outside of the striatum has been limited. Recent advances in fluorescent sensor technology and fiber photometry permit the measurement of dopamine binding correlates, which can divulge basic functions of dopamine signaling in non-striatal dopamine terminal regions, like the dorsal bed nucleus of the stria terminalis (dBNST)...

Sign-tracking rats show enhanced cue sensitivity before drug experience that predicts greater discrete cue-induced drug-seeking compared to goal-tracking or intermediate- rats. Cue-evoked dopamine in the nucleus Accumbens (NAc) is a neurobiological signature of sign-tracking behaviors. Here, we examine a critical regulator of the dopamine system; endocannabinoids, which bind the cannabinoid receptor-1 (CB1R) in the Ventral Tegmental Area (VTA) to control cue-evoked striatal dopamine levels. We use cell-type specific optogenetics, intra-VTA pharmacology and fiber photometry to test the hypothesis that VTA CB1R receptor signaling regulates NAc dopamine levels to control sign-tracking...

UNLABELLED: The survival of an organism is dependent on their ability to respond to cues in the environment. Such cues can attain control over behavior as a function of the value ascribed to them. Some individuals have an inherent tendency to attribute reward-paired cues with incentive motivational value, or incentive salience. For these individuals, termed sign-trackers, a discrete cue that precedes reward delivery becomes attractive and desirable in its own right. Prior work suggests that the behavior of sign-trackers is dopamine-dependent, and cue-elicited dopamine in the nucleus accumbens is believed to encode the incentive value of reward cues...

Sign-tracking is a behavior with relevance to cue-triggered relapse addiction, a Pavlovian conditioned approach behavior directed at the conditioned stimulus. The study examined one strategy for reducing the magnetic pull of drug-associated conditioned stimuli, using selective serotonin reuptake inhibitors (SSRIs) citalopram (0, 10, and 20 mg/kg), escitalopram (0, 10, and 20 mg/kg) and fluoxetine (0, 5, and 10 mg/kg). Male Sprague-Dawley rats were first trained in a standard sign-tracking task and then acutely administered these drugs in a series of three experiments...

Externalizing behaviors in childhood often predict impulse control disorders in adulthood; however, the underlying bio-behavioral risk factors are incompletely understood. In animals, the propensity to sign-track, or the degree to which incentive motivational value is attributed to reward cues, is associated with externalizing-type behaviors and deficits in executive control. Using a Pavlovian conditioned approach paradigm, we quantified sign-tracking in 40 healthy 9-12-year-olds. We also measured parent-reported externalizing behaviors and anticipatory neural activations to outcome-predicting cues using the monetary incentive delay fMRI task...

Sign-tracking (ST) describes the propensity to approach and contact a Pavlovian reward cue. By contrast, goal-trackers (GTs) respond to such a cue by retrieving the reward. These behaviors index the presence of opponent cognitive-motivational traits, with STs exhibiting attentional control deficits, behavior dominated by incentive motivational processes, and vulnerability for addictive drug taking. Attentional control deficits in STs were previously attributed to attenuated cholinergic signaling, resulting from deficient translocation of intracellular choline transporters (CHTs) into synaptosomal plasma membrane...

Individual differences in reward-related learning are relevant to many behavioral disorders. Sensory cues that predict reward can become incentive stimuli that adaptively support behavior, or alternatively, cause maladaptive behaviors. The spontaneously hypertensive rat (SHR) expresses a genetically determined elevated sensitivity to delay of reward, and has been extensively studied as a behavioral model for attention deficit hyperactivity disorder (ADHD). We investigated reward-related learning in the SHR, comparing them to Sprague-Dawley (SD) rats as a reference strain...

RATIONALE: Acetylcholinergic antagonists have shown some promise in reducing addiction-related behaviors in both preclinical and clinical studies. However, the psychological mechanisms by which these drugs are able to affect addictive behavior remain unclear. A particular key process for the development of addiction is the attribution of incentive salience to reward-related cues, which can be specifically measured in animals using a Pavlovian conditioned approach procedure. When confronted with a lever that predicts food delivery, some rats engage with the lever directly (i...

Most people sample addictive drugs, but use becomes disordered in only a small minority. Two important factors that influence susceptibility to addiction are individual differences in personality traits and biological sex. The influence of traits on addiction-like behavior is well-characterized in preclinical models of cocaine self-administration, but less is understood in regards to opioids. How biological sex influences trait susceptibility to opioid self-administration is likewise less studied than psychostimulants...

Sign tracking versus goal tracking in rats indicate vulnerability and resistance, respectively, to Pavlovian cue-evoked addictive drug taking and relapse. Here, we tested hypotheses predicting that the opponent cognitive-behavioral styles indexed by sign tracking versus goal tracking include variations in attentional performance which differentially depend on basal forebrain projection systems. Pavlovian Conditioned Approach (PCA) testing was used to identify male and female sign-trackers (STs) and goal-trackers (GTs), as well as rats with an intermediate phenotype (INTs)...

Relapse into addiction is often triggered by cues that have a Pavlovian association with drugs and drug-taking. Sign-tracking involves approach of and interaction with Pavlovian conditioned signals for appetitive events (as opposed to goal-tracking, which involves approach of the site of the appetitive events themselves) and may be important in understanding cue-driven relapse. Bupropion is an atypical antidepressant and smoking cessation aid with effects on dopamine and norepinephrine that may have some utility in reducing sign-tracking...

Sign-tracking, as a classically conditioned behavior, is of interest due to its relation to impulsivity and addiction. Caffeine affects the activity of neurotransmitters linked to sign-tracking such as dopamine and acetylcholine. As such, acute caffeine administration may enhance sign-tracking behavior. Caffeine was found to enhance measures of sign-tracking behavior in Sprague-Dawley rats in a sign/goal-tracking procedure. It is suggested that part of caffeine's effects on cognition may be due to its ability to enhance incentive salience in conditioned stimuli...

Model-free and model-based computations are argued to distinctly update action values that guide decision-making processes. It is not known, however, if these model-free and model-based reinforcement learning mechanisms recruited in operationally based, instrumental tasks parallel those engaged by Pavlovian based behavioral procedures. Recently, computational work has suggested that individual differences in the attribution of incentive salience to reward predictive cues, i.e., sign- and goal-tracking behaviors, are also governed by variations in model-free and model-based value representations that guide behavior...

Goal-tracking rats are sensitive to Pavlovian outcome devaluation while sign-tracking rats are devaluation insensitive. During outcome devaluation, goal-tracking (GT) rats flexibly modify responding to cues based on the current value of the associated outcome. However, sign-tracking (ST) rats rigidly respond to cues regardless of the current outcome value. Prior work demonstrated disconnection of the basolateral amygdala (BLA) and anterior insular cortex (aIC) decreased both goal- and sign-tracking behaviors...

Cue-based associative learning (i.e., Pavlovian conditioning) is a foundational component of behavior in almost all forms of animal life and may provide insight into individual differences in addiction liability. Cues can take on incentive-motivational properties (i.e., incentive salience) through Pavlovian learning. Extensive testing with non-human animals (primarily rats) has demonstrated significant variation among individuals in the behaviors this type of learning evokes. So-named "sign-trackers" and "goal-trackers" have been examined in many studies of non-human animals, but this work in humans is still a nascent area of research...

RATIONALE: Discriminative stimuli (DS) are cues that predict reward availability. DS are resistant to extinction and motivate drug seeking even after long periods of abstinence. Previous studies have demonstrated that sign-tracking (ST) and goal-tracking (GT) differences in Pavlovian approach predict distinct cue-modulated vulnerabilities to cocaine reinstatement. GT rats show heightened reinstatement to contextual and DS, while ST rats show heightened reinstatement to discrete stimuli...

Research shows cognitive and neurobiological overlap between sign-tracking [value-modulated attentional capture (VMAC) by response-irrelevant, discrete cues] and maladaptive behaviour (e.g. substance abuse). We investigated the neural correlates of sign-tracking in 20 adults using an additional singleton task (AST) and functional magnetic resonance imaging (fMRI). Participants responded to a target to win monetary reward, the amount of which was signalled by singleton type (reward cue: high value vs. low value)...

Sign-tracking is a well-known phenomenon in appetitive Pavlovian conditioning in which subjects approach the site of a conditioned stimulus (CS) associated with an appetitive unconditioned stimulus (US) even when the two are located separately. Control of sign-tracking may be important in rehabilitation from drug dependence to help ward off relapse. Recent studies have found success in using ketamine to reduce sign-tracking. In this study, we employed a similar but unscheduled drug, dextromethorphan (DXM), which affects many of the same molecular targets as ketamine, in an attempt to reduce sign-tracking in a standard paradigm...

Relapse-like behaviors have been measured in animals using the Pavlovian conditioned approach (PCA) model. During conditioning, a reward is paired with a novel, neutral cue (unconditioned stimulus; UCS). Repeated pairing of the UCS with a salient reward can elicit a conditioned response (CR). Sign tracking (STing) is a CR to the newly conditioned stimulus (CS). Subjects that show a propensity to sign-tracker (ST) show greater rates of drug-taking behaviors. The vast majority of research in sign tracking is in a male species...

We have previously shown that rats emit high-frequency 50 kHz ultrasonic vocalizations (USV) during sign- and goal-tracking in a common Pavlovian conditioned approach task. Such 50 kHz calls are probably related to positive affect and are associated with meso-limbic dopamine function. In humans, the CACNA1C gene, encoding for the α1C subunit of the L-type voltage-gated calcium channel CaV 1.2, is implicated in several mental disorders, including mood disorders associated with altered dopamine signaling. In the present study, we investigated sign- and goal-tracking behavior and the emission of 50 kHz USV in Cacna1c haploinsufficent rats in a task where food pellet delivery is signaled by an appearance of an otherwise inoperable lever...