Increased locomotor activity in estrogen-treated ovariectomized rats is associated with nucleus accumbens dopamine and is not reduced by dietary sodium deprivation.

Estrogens are well known to increase locomotor activity in laboratory rodents; however, the underlying mechanism remains unclear. We used voluntary wheel running by female rats as an index of locomotor behavior to investigate this issue. We first determined whether the estrogen-induced increase in locomotion was susceptible to inhibition by a physiological challenge, and next whether it was associated with dopaminergic activation in the central reward area, nucleus accumbens. Ovariectomized rats were given estradiol or the oil vehicle and housed in cages with or without running wheels. All rats were given regular rodent chow for 1 week, a sodium-deficient diet for the next week, and then were returned to a regular diet for another week. At the end of the last week, all rats were killed, brains were extracted and dopamine levels in the nucleus accumbens were measured. As expected, estradiol treatment increased distance run. Surprisingly, dietary sodium deprivation further increased running, but this appeared to be related to experience with wheel running, rather than to sodium deprivation, per se. Dopamine was greater in the nucleus accumbens of estradiol-treated rats that ran compared to all other groups. Thus, the estrogen-induced increase in locomotion is a robust phenomenon that is not inhibited by a body sodium challenge and is associated with elevated levels of dopamine in reward pathways. These findings raise the possibility that the estrogen-induced increase in locomotor activity, which occurs during a hormonal milieu conducive to reproduction, may reflect mate-seeking behavior and, thereby, maximize reproductive success.