Ovarian hormonal state at exercise initiation interacts with nigrostriatal circuitry to determine long-term voluntary exercise behavior

Despite the well-established health benefits of exercise, adherence to physical activity remains low, highlighting the need to identify biological factors that regulate the initiation and persistence of exercise behavior. Here, we tested whether ovarian hormone state at the onset of voluntary wheel running (VWR) influences both immediate and long-term exercise behavior in female rats. Females that initiated VWR during proestrus (Pro) ran farther, spent more time running, and ran at higher speeds on the first day of wheel access than females initiating VWR outside of Pro. Remarkably, initiating VWR during Pro also produced persistent increases in running distance, duration, speed, and escalation across subsequent weeks, despite normal cycling through other estrous phases. In contrast, exogenous estradiol (E2) administered at VWR initiation did not alter day-1 behavior, but increased running distance and duration across subsequent weeks without affecting running speed or escalation. To determine whether dorsal striatal dopamine contributes to these effects, we inhibited the substantia nigra (SN) to dorsolateral striatum (DLS) pathway on the first day of VWR. This manipulation reduced the immediate and long-term effects of initiating VWR during Pro on running duration and distance but not speed or escalation. These findings identify behavioral initiation as a critical window during which hormones and nigrostriatal signaling influence future engagement in physical activity. Furthermore, analysis of individual components of VWR architecture reveals that distinct features of VWR behavior can be dissociated mechanistically and thus could be used to investigate separate motivational processes underlying physical activity.