Theta oscillations vary with local response rate and are moderated by the dopamine-depleting agent, tetrabenazine,...

The nucleus accumbens plays a pivotal role in goal-directed behaviors, receiving inputs from prefrontal cortex and hippocampus. We investigated local field potential activity in all three areas in awake-behaving male Sprague-Dawley rats performing a high-effort lever pressing task for food reinforcement (fixed-ratio, FR40 schedule). Using a within-subject design, we administered a VMAT-2 inhibitor tetrabenazine (TBZ), a dopamine-depleting agent that suppresses the exertion of effort in instrumental behaviors and induces a low-effort bias on choice tasks. Tetrabenazine substantially reduced lever pressing compared with vehicle in rats responding on the FR40 schedule, and we observed that TBZ significantly decreased theta peak frequency and power (6-12 Hz). Theta frequency and power both decreased with higher local rates of responding, especially in dorsal hippocampus, and this relationship is moderated by TBZ, marking its modulatory effects on neural dynamics during exertion of effort. There is substantial variability between animals in both the TBZ-induced suppression of lever pressing and the relationship between theta power and local press rate. We determined that the behavioral effects of TBZ were correlated with these neurophysiological changes across animals. Taken together, these findings demonstrate how TBZ may affect both theta dynamics and effortful behavior and suggest that the amplitude and frequency of theta band may vary with exertion of effort in motivated behavior.