Basolateral amygdala dopamine in addiction-related learning strategies

Project Summary Environmental stimuli (“cues” – sensory information such as sights, sounds, and smells) help organize reward seeking and decision making. In disease states like addiction drug-related cues can acquire powerful control over behavior, promoting exaggerated drug intake and relapse. Cues vary in their sensory modality, temporal profile, and their relationship with one another and behavior. Within this complex sensory landscape, not all individuals respond the same way to reward cues. For example, some rats, when trained to associate a discrete, localizable cue with a food reward in a Pavlovian conditioning procedure, develop cue-directed approach behavior, known at sign tracking. Other rats develop approach behavior directed at the location of reward delivery, termed goal tracking. In preliminary studies we expand this notion to show that discrete versus state-based drug-associated cues preferentially evoke relapse of drug seeking in different subsets of rats. Here, we will investigate how Pavlovian reward-learning strategies (e.g., sign versus goal tracking) predict an individual’s unique relapse trigger, for greater understanding of vulnerability to addiction. To explore the neural mechanisms of these behaviors, we focus on the basolateral amygdala (BLA), a critical brain site for the integration of sensory and emotional information to guide associative learning and goal-directed behavior. Dopamine neurons, in addition to their classic striatal targets, also project strongly to the BLA, where densely expressed D1-type dopamine receptors reside. Here, we will examine the role of BLA dopamine and D1 neurons in the emergence and expression of reward-based learning and addiction-like behaviors. In three Aims, we will test the central hypothesis that individual differences in reward learning strategies reflect biased responsivity to proximal vs state-based sensory information, resulting in unique vulnerabilities to addiction-like behavior that are encoded and controlled by dopamine signaling within the BLA.