Publications

Pavlovian learning processes can render cues and contexts associated with drug-taking experiences into powerful motivators, such that exposure to such stimuli can elicit drug-seeking behavior and relapse. However, there is considerable individual variation in the extent to which a reward cue can gain control over behavior. The sign-tracker (ST)/ goal-tracker (GT) animal model provides a means to capture this individual variation and study the underlying psychological and neurobiological processes. For both phenotypes, a reward cue acquires predictive value and elicits a conditioned response, but only for STs does it also acquire incentive value. That is, for STs the reward cue becomes an incentive stimulus, or a “motivational magnet.” Relative to GTs, STs are also more impulsive on tests of impulsive action, show greater motivation to work for cocaine, and show greater drug-seeking behavior during tests for cue- and cocaine-induced reinstatement. Using this model, we are able to interrogate the neurobiological mechanisms underlying both the propensity to attribute incentive salience to reward cues and the associated addiction-related behaviors. Research thus far has shown that sign-tracking is a dopamine-dependent process that relies on subcortical circuitry, including the hypothalamic-thalamic-striatal pathway. Conversely, goal-tracking behavior is driven by cortical cognitive processes. Furthermore, differences in neurotransmitter systems, including dopamine and acetylcholine, appear to contribute to the distinct neural circuits mediating sign- and goal-tracking behavior. Taken together, we believe that an imbalance between “top-down” cortical processing relative to “bottom-up” subcortical processing is responsible for the behavioral phenotypes of sign- and goal-trackers, including addiction vulnerability and relapse propensity.

Clinical and preclinical findings suggest that individuals with abnormal responses to reward cues (stimuli associated with reward) may be at risk for maladaptive behaviors including obesity, addiction and depression. Our objective was to develop a new paradigm for producing appetitive conditioning using primary (food) rewards in humans, and investigate the equivalency of several outcomes previously used to measure appetitive responses to conditioned cues. We used an individualized food reward, and multimodal subjective, psychophysiological and behavioral measures of appetitive responses to a conditioned stimulus (CS) that predicted delivery of that food. We tested convergence among these measures of appetitive response, and relationships between these measures and action impulsivity, a putative correlate of appetitive conditioning. 90 healthy young adults participated. Although the paradigm produced robust appetitive conditioning in some measures, particularly psychophysiological ones, there were not strong correlations among measures of appetitive responses to the CS, as would be expected if they indexed a single underlying process. In addition, there was only one measure that related to impulsivity. These results provide important information for translational researchers interested in appetitive conditioning, suggesting that various measures of appetitive conditioning cannot be treated interchangeably.

The paraventricular nucleus of the thalamus (PVT) has been shown to mediate cue-motivated behaviors, such as sign- and goal-tracking, as well as reinstatement of drug-seeking behavior. However, the role of the PVT in mediating individual variation in cue-induced drug-seeking behavior remains unknown.

Cues or stimuli in the environment can guide behavior in adaptive ways, bringing one in close proximity to valuable resources (for example, food). For some individuals, however, environmental stimuli may acquire inordinate control over behavior and elicit maladaptive tendencies or intrusive thoughts. Thus, the way an individual responds to cues in the environment may be a key determinant of psychopathology. For example, in addiction, relapse is most often triggered by exposure to stimuli (for example, paraphernalia or places) previously associated with the drug-taking experience, and people suffering from post-traumatic stress disorder (PTSD) experience extreme anxiety or flashbacks upon exposure to stimuli reminiscent of a traumatic event. Furthermore, in patients with schizophrenia, psychosis is believed to result from aberrant attribution of motivational salience to environmental stimuli (Kapur, 2003). Such stimuli are able to elicit complex emotional and motivational states via Pavlovian learning, and in recent years we have come to rely on an animal model to better understand these processes (for review see Robinson et al, 2014).