Hormone-dependent sexual responses of female mice in response to manual genital stimulation.

Although copulatory behavior is thought to have a strong innate basis in mice, there is also clear evidence that sexual experience shapes its expression. Reinforcement of behavior through rewarding genital tactile stimulation is a primary candidate mechanism for this modification. In rats, manual tactile clitoral stimulation is rewarding only when it is temporally distributed, which is hypothesized to result from an innate preference for species-typical copulatory patterning. Here we test this hypothesis using mice, which have a temporal copulatory pattern which is distinctly less temporally distributed than that of rats. Female mice received manual clitoral stimulation which was either temporally continuous every second, or stimulation which was temporally distributed, occurring every 5 s, This pattern of stimulation was paired with environmental cues in a conditioned place preference apparatus to assess reward. Neural activation in response to this stimulation was evaluated by measuring FOS immunoreactivity. Results indicated that both temporal patterns of clitoral stimulation were rewarding, but that continuous stimulation better reproduced brain activation associated with sexual reward. Furthermore, continuous, but not distributed stimulation elicited a lordosis response in some females, and this response increased within and across days. Sexual reward, neural activation and lordosis resulting from tactile genital stimulation were eliminated by ovariectomy and restored with combined 17β-estradiol and progesterone treatment but not 17β-estradiol treatment alone. These observations are consistent with the hypothesis that sexual reward resulting from species-typical genital tactile stimulation has a permissive effect on copulatory behavior of female mice.