Dopamine in the Dorsal Bed Nucleus of Stria Terminalis signals Pavlovian sign-tracking and reward violations

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 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). The dBNST receives dense dopaminergic input from several regions including the ventral tegmental area, ventral periacqueductal gray, and substantia nigra. Here, we record fluorescent GRABDA signals in the dBNST during a Pavlovian lever autoshaping task that has established individual differences in cue-evoked striatal dopamine signals in sign- and goal-tracking rats. We observe greater Pavlovian cue-evoked dBNST GRABDA signals in sign-tracking (ST) compared to goal-tracking/intermediate (GT/INT) rats. We find the magnitude of cue-evoked dBNST GRABDA signals decrease immediately following reinforcer-specific satiety. When we deliver unexpected reward or omit expected reward, we find that dBNST dopamine signals encode bidirectional reward prediction errors in GT/INT rats, but only positive prediction errors in ST rats. Since sign- and goal-tracking approach strategies are associated with distinct drug relapse vulnerabilities, we examined the effects of experimenter-administered and self-administered fentanyl on dBNST dopamine associative encoding. Systemic fentanyl injections do not disrupt dBNST cue discrimination but generally potentiate dBNST dopamine signals. Fentanyl self-administration experience is sufficient to reverse reward seeking and dBNST dopamine signals, which discriminate fentanyl-associated active vs. inactive lever pressing under extinction conditions. These results reveal multiple dBNST dopamine correlates of learning and motivation that depend on the Pavlovian approach strategy employed.