Dopamine and Calcium Dynamics in the Nucleus Accumbens Core during Food Seeking

Extinction-reinstatement paradigms have been used to study reward-seeking for both food and drug rewards. The nucleus accumbens (NAc) is of particular interest in reinstatement due to its ability to energize motivated behavior. Previous work found that suppression of neuronal activity or dopamine signaling in NAc reduces reinstatement of food-seeking. Here we used fiber photometry and sensor multiplexing (red-shifted dopamine sensor and genetically-encoded calcium indicator) to measure dopamine and calcium in NAc core of male and female rats on each day of an extinction-reinstatement paradigm with food reward to determine how signals vary across task phases. During self-administration training, we detected positive dopamine transients that initially followed lever pressing but moved earlier in time as training progressed. A post-press dopamine decrease also emerged with training. For calcium, a decrease from baseline occurred after the press and became more prominent across training. Both patterns were reduced in the first extinction session, with no deflections from baseline detected in dopamine or calcium traces in the last extinction session. During reinstatement tests primed with either cue or combined food reward and cue presentation, we observed positive calcium and dopamine responses that differed significantly from the signals measured in the last extinction session. While multiplexing has been validated by prior studies, ours is the first to simultaneously record dopamine and calcium during an extinction-reinstatement task. The results provide new information about changing relationships between these signals across task phases, setting the stage for exploring their behavioral significance and mechanisms that may link the two signals.