Cue-triggered reward seeking: The role of dopamine and corticotropin releasing factor in the bed nucleus of stria terminalis
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Abstract
Survival depends on learning associations between reward and reward predictive cues. Cues associated with rewards, however, can also reinforce maladaptive behaviors. Pharmacological inactivation of the bed nucleus of stria terminalis (BNST) reduces cue-induced drug reinstatement. Neural signaling in the BNST underlying cues-maintained motivated behavior remain poorly understood. The overarching objective of this dissertation is to identify the role of key neuromodulators in the BNST during cue-triggered reward seeking. In Chapter 2, I focus on corticotropin releasing factor (CRF) and its contribution in incubation of fentanyl seeking after forced abstinence. I find that antagonizing CRF receptors in the BNST results in reduced incubation of fentanyl craving and encourages disengagement from lever pressing for cues in abstinence. In Chapter 3, I use fiber photometry in combination with the dopamine sensor GRABDA to measure real-time dopamine signals when rats are engaged in a Pavlovian Lever Autoshaping task. I first demonstrate that Pavlovian cue-evoked dorsal BNST GRABDA signals are enhanced in rats that assign incentive motivational properties to reward cues. I next characterize GRABDA signals in reward prediction error, satiety, systemic fentanyl administration, and during responding for fentanyl-associated cues. Collectively, these findings establish a relationship for BNST CRF and dopamine in cue-evoked self-motivated behaviors.