Elucidating the interaction between stress- and reward-mechanisms mediating individual differences in cue motivated behaviors

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ABSTRACT Through associative learning processes, cues in the environment become predictors of biologically relevant stimuli (e.g. food). However, when attributed with incentive value, such cues can become powerful motivators of maladaptive behavior. For example, addicts often relapse upon exposure to cues (e.g. people, paraphernalia) previously associated with the drug-taking experience. Using an animal model that captures individual variation in the propensity to attribute incentive value to reward cues, we can investigate the neurobiological mechanisms underlying cue-motivated psychopathologies like addiction. Rats that undergo Pavlovian training, consisting of cue presentation followed by delivery of a food reward, will often develop either a sign- or goal-tracking conditioned response. For both sign-trackers (ST) and goal-trackers (GT) the cue attains predictive value, but for ST the cue also attains incentive value. The attribution of incentive value to the cue transforms it into a “motivational magnet”, rendering it attractive and desirable for ST, but not GT. It has been shown that different brain circuits are engaged in response to the cue in ST vs. GT, and that dopamine (DA) is necessary for incentive (i.e. sign-tracking), but not predictive (i.e. goal-tracking) learning processes. However, to date, little has been investigated beyond the traditional “motive” circuit in ST and GT. To expand our knowledge in this regard, I will study the interaction between stress- and reward-systems in ST and GT rats. DA has long been known to interact with corticosterone (CORT), a primary mediator of the stress-response, and in turn potentiate motivated behaviors. Given that cue-elicited DA and CORT profiles differ between ST and GT, the overarching hypothesis of my work is that DA- and CORT-integrative circuits mediate individual differences in the attribution of incentive value to reward cues. The goal of the proposed work is to identify an intersection between stress- and reward- systems that drives distinct behavioral responses to environmental stimuli. To do so, I will combine and become proficient with endocrine, neurochemical, pharmacological, genetic, and behavioral approaches and analyses. This work will elucidate potential mechanisms that may render individuals more susceptible to cue-driven psychopathologies, and provide comprehensive training towards my independent scientific growth.